review article fluorescent gold nanoclusters: synthesis and … · 2019. 7. 31. · fluorescent...

Review ArticleFluorescent Gold Nanoclusters Synthesisand Recent Biological Application

Xiaochao Qu Yichen Li Lei Li Yanran Wang Jingning Liang and Jimin Liang

School of Life Science and Technology Xidian University Xirsquoan Shannxi 710071 China

Correspondence should be addressed to Xiaochao Qu xiaochaoqugmailcom

Received 16 September 2014 Accepted 14 January 2015

Academic Editor Rajesh Naik

Copyright copy 2015 Xiaochao Qu et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Fluorescent gold nanoclusters (AuNCs) have been extensively studied due to their unique construction and distinctive propertieswhich place them between single metal atoms and larger nanoparticles The dimension of AuNCs is comparable to the Fermiwavelength of electrons which lead to size-dependent fluorescence and other molecule-like properties In this review wesummarize various synthesis strategies of fluorescent AuNCs and recent advances of biological applications such as biosensingbiolabeling and bioimaging The synthetic methods are considered as two routes ldquoAtoms to Clustersrdquo and ldquoNanoparticles toClustersrdquo The surface functionalization of AuNCs is described as the precondition for making future bioapplications possiblewhich can eventually influence their stability biocompatibility and other properties And then we focus on the recent advances ofAuNCs-based applications in biological sensing biolabeling and bioimaging and finally discuss the current challenges of AuNCsin controllable synthesis and biological application

1 Introduction

The word ldquonanordquo is for describing something which occurswith size on nanometer range [1] The worldwide emergenceof nanoscale technology and engineering was marked bythe announcement of the National Nanotechnology Initiative(NNI) in January 2000 [2] Nanotechnology which becamean emerging and promising research field in the past decadesis the combination of medicine chemistry physics andbiology [3] This multidisciplinary technology is considereddedicating to assemble molecules into objects and reversethis process The confluence of biology and nanotechnol-ogy is defined as nanobiotechnology which is a field thatinvestigates biosystems and creates new biomaterials usingnanoscale principles and techniques [2] The nanostructurematerials in biology and biomedical field can be useful toolsfor biosensing cell labeling and molecular imaging

Gold is the most extensively studied material amongworldwide groups due to its stable chemical property facilesynthesis and nontoxicity Gold on bulk- or molecular-rangeis highly stable however gold nanoparticles (NPs) exhibitdistinctive properties which differ from others such as their

surface plasmon resonance (SPR) effect size-depending elec-tronic properties and their photothermal effect in biologicaltherapy [4] For these fascinating aspects gold NPs have beenconsidered as the keymaterials of nanoscience and nanotech-nology in recent years Due to quantum confinement effectsof gold nanoparticles with a dimension below 2 nm they aretoo small to support surface plasmon resonance effect [5]The noble metal nanomaterials (which we call them goldnanoclusters) are composed of several to roughly a hundredatoms [6 7]The dimension occurringwith gold nanoclusters(AuNCs) is comparable to the Fermi wavelength of electrons[8] which place them between single metal atoms and largernanoparticles [9] Due to the strong quantum confinementeffect of free electrons in the particles the continuous densityof states breaks up into discrete energy levels These lead tosize-dependent fluorescence and other attractive molecule-like properties such as facile surface tailor ability and colortenability [10ndash13]

As to size-dependent fluorescence the photophysicalproperties of AuNCs are dictated by their sizes and shapesRecent advances make it much easier to synthesize water-soluble AuNCs with tunable size or emission colors AuNCs

Hindawi Publishing CorporationJournal of NanomaterialsVolume 2015 Article ID 784097 23 pageshttpdxdoiorg1011552015784097

2 Journal of Nanomaterials

has an extremely high surface-to-volume ratio which canmake the NCs for further surface modification and control-lable bioconjugation With all the above properties AuNCscan be used in a wide range of applications such as biode-tection [14] biosensing [14] biological labeling [15ndash17] andbioimaging [18]

When fluorophores absorb light with a particular wave-length fluorophoreswill then emit energy in a formof fluores-cence equaling to the energy difference between the excitedstate and the ground state Fluorescent probes are the keyfactor in biological fluorescent measurement In last decadesthere are several different classes of fluorescent labels organicfluorophores such as cyanine dyes and fluorescein the rareearth NPs (quantum dots) [19] upconverting NPs andnovel fluorescent dye-doped core-shell nanobeads But theuse of these labels is limited by the poor photostabilitylarge physical size and toxicity of heavy metals [17] Onthe contrary AuNCs show strong photoluminescence goodphotostability and high emission rates large Stokes shift andsize-dependent tunable fluorescence for which they can bemade as an optimum nanomaterial for biological imaginganalysis and sensing Moreover the surfaces of AuNCspossess a subnanometer dimension color tenability facilesynthesis and low toxicity [20 21] Compared with commonfluorophores these advantages establish them to be a novelultrasmall fluorophores in biomedicine application [22ndash24]

In this review we firstly will discuss the origin of fluores-cence of AuNCs Then we will summarize general synthesisstrategies of AuNCs and describe their distinctive propertieswhich are followed by highlighting their fascinating photolu-minescence properties In the second part we will discuss therecent advances of AuNCs-based application to the biologicallabeling and fluorescent imaging In the final section we willgive a brief outlook on the challenges and prospective forfuture research of AuNCs

2 Gold Nanoclusters FluorescenceProperty and Synthetic Method

21 Fluorescence Mechanism of AuNCs Gold nanomaterialscan be broadly categorized into two kinds according to theirdimensions gold nanoparticles and gold nanoclusters Zhenghas introduced the differences in structures and other prop-erties between these two gold nanomaterials [25] As hemen-tioned gold nanoparticles which sizes are close to the wave-length of light have similar optical properties to bulk goldWhat is more the collective oscillation of conduction elec-trons on the surface of gold nanoparticles can interact withlight and generate SPR effect when the frequency of oscil-lating electrons matches the frequency of incident photonsAnd when the gold nanoparticles have a dimension in 3ndash100 nm the SPR band locates in the visible light region whichwill lead to some size-dependent effects of gold NPs Theinteraction between nanoparticles the dielectric mediumand the protective ligands also has influences on the SPReffect of gold NPs

When size of gold nanomaterials is smaller than 3 nm thegold nanoclusters possess some distinguished properties dueto their ultrasmall dimension and special structure Because

the energy level spacing is inversely proportional to the radiusof AuNCs AuNCs with a dimension close to Fermi wave-length of an electron possess size-dependent electronic struc-ture [26]TheAuNCswe are discussing in this review are sub-nanoscale nanoparticles which have a gold center containinga countable number of gold atoms So AuNCs are consideredas superatoms or molecular-like species For these reasonsthe energy level spacing and free electronic density of AuNCsare the key factors of transition energy of AuNCs When theenergy level spacing is large enough the free electrons behav-ior can be observed in the discrete energy levels [27] Accord-ing to the structural analysis of Jinrsquos group the fluorescence ofAuNCs originates from the LUMO-HOMO transition [28]To sum up the distinct optical properties (absorption andfluorescence) ofmolecular-like AuNCs aremainly affected bytheir ultrasmall size and corresponding electronic structure

In addition to the ultrasmall size the ligands used forAuNCs preparation also have impacts on their fluorescenceproperties [5] Ligands play very important roles in theformation of AuNCs as protective agents which can preventthe superatoms from aggregation and then keep the size-dependent fluorescence property As for the demonstrationthat Jin and coworkers mentioned surface ligands of AuNCsnot only can be used as capping agent but also largelyaffect the fluorescence of AuNCs by charging transfer fromsurface ligand to the gold core When the surface ligandshave strong electron donation capability the fluorescencecan be enhanced And the ligands with electron-rich atomsor groups have been found as a very effective choice forpromising surface ligand of AuNCs to enhance the fluores-cence In this paper we will discuss the synthesis of AuNCsby using different ligands such as glutathione dendrimerspolymers and protein the as-prepared AuNCs based on dif-ferent synthetic methods have various fluorescence quantumyield (QY) Lots of researches have been carried out on theorigin of fluorescence from AuNCs and the enhancementof fluorescence QY for the practical application such asbiological labeling sensing and imaging In this section wehave summarized the different fluorescence QYs of AuNCswith different synthetic routes (Table 1)

22 Synthetic Methods of AuNCs Small gold nanoclusterswith robust quantum effect have been extensively investi-gated The synthesis of AuNCs experiences several stages Inthe early time the research was focused on gas state metalclusters [29] Since these metal clusters in the gas phase wereshort-lived and hard to be functionalized a novel methodsolution-phase synthesis arose in the 1980s [30 31] Thesesynthetic strategies lead to gold nanoclusters with enhancedstability and excellent physicochemical properties

Since Brust et al reported the synthesis of monolayerprotected metal nanoparticles several novel advances haveemerged in the field of metal nanoclusters especially in thefield of thiol-containing AuNCs During the decades thesynthetic strategies were generally considered as two routesldquoAtoms to Clustersrdquo and ldquoNanoparticles to Clustersrdquo Theapproach of ldquoAtoms to Clustersrdquo is to reduce the gold ionsinto zerovalent atoms and then AuNCs are formed with thenucleation of the Au atoms However the gold precursors

Journal of Nanomaterials 3

Table 1 Summary of fluorescence QYs of AuNCs obtained by different synthetic approaches

Synthesis Fluorescence QYs ReferencesProtected by monolayers of glutathione (35 plusmn 10) times 10minus3 [32]Alkanethiol ligands 11-mercaptoundecanoic acid (11-MUA) as stabilizer 31 times 10minus2 [33]Poly(amidoamine) (PAMAM) dendrimers as stabilizer and capping agent 41 plusmn 5 [34]Pentaerythritol tetrakis(3-mercaptopropionate)-terminated Polymethacrylic acid(PTMP-pMAA) as capping agent 3 [35]

Employed poly(N-vinylpyrrolidone) (PVP) as stabilizer of the gold clusters 125 [36]Bovine serum albumin molecules as templates and reductants sim6 [37]Bovine pancreatic ribonuclease A (RNase-A) as the biotemplate sim12 [38]DNA as template to prepare goldsilver nanoclusters from Au3+ Ag+ and DNA(51015840-CCCTTAATCCCC-31015840) 45 [39]

Employing L-34-dihydroxyphenylalanine (L-DOPA) as a reducingcapping reagent 17 [40]D-penicillamine as capping agent 13 plusmn 03 [41]Mercapto-9-propyladenine as capping agent 12 [42]NN-dimethylformamide as a weak reducing agent as well as stabilizing ligand 1428 [43]Dissociation process of glutathione-gold(I) polymers in aqueous solution 40 plusmn 04 [44]GSH as reductant to form Au(I)-thiolate complexes and the aggregation ofAu(I)-thiolate complexes on the Au(0) to form Au(0)Au(I)-thiolate NCs sim15 [45]

11-Mercaptoundecanoic acid (11-MUA) as the protecting group to reduce Au3+ withNaBH4 in methanol solutions sim692 [46]

Polyethylene glycol (PEG) appended with lipoic acid (LA) anchoring groups asmodular ligands 14 [47]

can be reduced into gold nanoparticles easier than intonanoclusters due to the possibility of AuNCs to aggregateIn order to solve the problem some kinds of ligands shouldbe used for surface modification Moreover the protectiveligand capped on the surface can enhance the fluorescenteffectThese show that choosing appropriate ligands is the keyfactor in stabilizing cluster from aggregationThe other routefor synthesizing the AuNCs is ldquoNanoparticles to Clustersrdquoroute Pradeep and coworker used excess MSA ligands intoluene to etch (MSA-) protected large Ag nanoparticles intofluorescent Ag NCs [48] Recently some advances have beenreported [49ndash51] to form more stable monodisperse andhighly fluorescent AuNCs

221 ldquoAtoms to Clustersrdquo Route

(1) Template-Based Synthesis Methods AuNCs with ultrafinesize and nontoxicity are very attractive for biolabeling andbioimaging application For the reason of low fluorescentQY (10minus4ndash10minus1) of thiol-protected AuNCs Dicksonrsquos groupdeveloped NCs exhibiting sim40 QY by dendrimers-assistedmethod in the early 2000s [34] This synthesis can effec-tively enhance the fluorescent effect of AuNCs with a fairlylong reaction time According to the first template-assistedtechniques a series of templates such as polymers [35 52]proteins [53 54] dendrimers [55] and DNA [56 57] havebeen investigated for the synthetic method of AuNCs Com-pared with other synthetic techniques template-protectedtechniques use mild reductant in the presence of strongstabilizer The decreased clustering rate provides efficientsequestering by stabilizers

(i) Dendrimers Dendrimers-encapsulated AuNCs exhibitedstrong fluorescence in the range from blue to NIR region byadjusting the generation of PAMAM and the ratio betweengold and the template [55] Water-soluble monodispersehighly fluorescent Au

8

NCs had been synthesized by usingthe fourth generation of polyamidoamine (G4-OHPAMAM)dendrimers as reduction agent and stabilizer [58 59] byDickson and coworkers in the early 2000s [34 55] The as-prepared AuNCs exhibit a strong fluorescence (QYsim40)with an intensity of 100-fold higher than AuNCs preparedby other methods possessing strong blue luminescence withexcitation and emission peak at 385 nm and 450 nm respec-tively shown in Figure 1

Using charged PAMAM dendrimers of generation 6ndash9 toprepare size-tunable fluorescent AuNCs in water have beenreported The production have been characterized by a set ofmethods such as tranmission electron microscopy (TEM) todemonstrate gold atoms encapsulated by dendrimers In 2007Bao et al unveiled a newmethod for synthesizing nontoxicityhighly stableAuNCs by using amild reduction agent-ascorbicacid or no reductant at physiological temperature [60] Thisapproach produced highly green and red emission AuNCswithout forming large gold nanoparticles Lin and coworkers[61] exploited an amphipathic microcavity-template forsequestering gold ions and synthesizingAuNCswith highQY(20ndash60) through microwave irradiation In this strategythe fourth generation PAMAM with amine-terminatedgroups (G4NH2) had a more hydrophilic microcavity thanhydroxyl-terminated G4OH PAMAM which led to thepolarity-dependent ion-pair association (AuCl

4

G4NH2

pairand AuBr

4

G4OH pair) The strong ion-pair association was


15000

10000

5000

0

400300 500 600 700

Wavelength (nm)

Inte

nsity

(a)

(b)

Figure 1 (a) Excitation and emission spectra of G4-OH PAMAM-templated AuNCs (b) Emission from AuNCs under long-wave-length UV lamp irradiation (366 nm) Reprinted with permissionfrom [34] copy2003 American Chemical Society

capable of enhancing the quantum efficiency of AuNCs andthe precise control of the reaction temperature assisted bymicrowave irradiation could also lead to the same effects

(ii) Polymers Polymers are widespread macromolecule withabundant functional groups which have potential to betemplates for synthesizing AuNCs [62 63] Using polymersto prepare AuNCs has been studied by several groups Forexample AuNCs protected by multivalent polymers weresynthesized by ligand exchange with dodecylamine-cappedgold nanoparticles [64] The ligand-induced etching methodleads to fluorescent AuNCs with a relatively low QY (10ndash20) The size of polymer-depended AuNCs is related toseveral factors such as the structure of polymer the nature ofpolymer functional group and the ratio of gold to polymer[35 65 66] A switch over nonfluorescent to fluorescentpolymer-capped AuNCs (core diameters 11ndash17 nm) can befinely tuned by adjusting the ratio of gold-to-polymer asreported by Cooper et al Moreover Gonzalez et al havediscovered a new simple method for preparing AuNCsprotected by poly(N-vinylpyrrolidone) (PVP) which possessthe fluorescent and magnetic features [36] In this methodan electrochemical synthesis has been used to pursue amuch simpler and quicker synthetic route Most recentlyJiang and coworkers have developed novel hybrid nanogelsbased on the NIR fluorescent AuNCs and poly(acrylic acid)(PAA) [67] The core-hollow and shell-porous PAA nanogelswere employed as templates followed by in situ reductionof HAuCl

4

in water to synthesize AuNCs-encapsulated PPAhybrid nanogels The PAA nanogels were prepared by thepolymerization of acrylic acid monomer and thenmixing theproducts with cysteamine water solution through interactionof COOminus group of PAA and NH

2

+ of cysteamine Au3+ ionswere subsequently added and reduced by thiols of cysteamineso as to encapsulate Au+ into the cavities of PAA nanogelsFinally NaBH

4

was chosen to reduce theAu ions intoAuNCsshown in Figure 2 This AuNCs entrapped in PAA nanogels

Tumor

Cysteamine

NIR

Gold cluster-PAA hybrid nanogels

HAuCl4 NaBH4

Figure 2 Schematic of synthetic method of gold cluster-encap-sulated PAA hybrid nanogels Reprinted with permission from [67]copy2013 American Chemical Society

BSA AuCl4

BSA-Au NC

Incubate 12h

+ NaOH

Incubate 2min

+

BSA-Au ion complex

Figure 3 Schematic of the formation of BSA-templated AuNCsReprinted with permission from [37] copy2009 American ChemicalSociety

possessed the NIR fluorescent property with deep tissuepenetration which was suitable for NIR live imaging

(iii) Proteins Proteins as biological macromolecules havecertain configuration and spaces and can be utilized as tem-plates for preparing fluorescent AuNCs Xie and coworkershave developed a class ldquogreenrdquo synthesize method to prepareprotein-directed AuNCs [37] In this method a facile one-pot ldquogreenrdquo synthetic technique was developed based ona common commercially available protein bovine serumalbumin (BSA) as shown in Figure 3

BSA a plasma protein existing in abundance was selectedas the model protein for the formation of AuNCs becauseof its stability lack of effect and low cost Similar to thebiomineralization behavior in nature the Au3+ ions wereadded to the aqueous BSA solution to be reduced toAu+ withthe help of tyrosine residues on the protein and then metalions were sequestered and entrapped by thiol groups of theproteinThe as-prepared AuNCswere stable at the physiolog-ical temperature and PH with a QYsim6 The as-synthesizedBSA-AuNCs have 25 gold atoms in the core which exhibitred emission (maximum of emission wavelength locatesin 640 nm) excellent stability good biocompatibility andeasy surface modification This striking work is not only


a novel method for creating highly fluorescent AuNCs buta promising protocol can be used for the other proteins andnoble metals Following to this report many groups studiedthis ldquogreenrdquo synthetic route with other bioactive proteins suchas insulin [68ndash70] lysozyme [71] transferrin [72] and eggwhite proteins [53] Chou et al have firstly selected insulin asthe template for synthesizing the fluorescent AuNCs The as-prepared insulin-AuNCs are applicable for fluorescent imag-ing CT and in vivo blood-glucose regulation As innovativeimaging technique involving insulin it should be extensivelystudied in biolabeling and bioimaging application The useof BSA as a reductant and stabilizer has enlightened Lu et alto find some proteins expect BSA for preparing AuNCsThey have discovered a way to prepare highly fluorescentAuNCs by using lysozyme as reductant and stabilizer Theas-synthesized lysozyme gold fluorescent NCs (LsGFC) havea diameter of sim1 nm and emission wavelength centered at657 nm which also can be specifically quenched by Hg2+Very recently chicken egg white (CEW) which is abundantfor being available and extremely cheap has been exploitedas a template for synthesizing AuNCs by Geckerler et al Inthemethod researchers developed a green rapid synthesis ofAuNCs using CEW at physiological temperature (37∘C) withpHsim11 Under alkaline conditions tyrosine and tryptophanare predominantly responsible for reduction of Au3+ ionsand obtained highly fluorescent water-soluble AuNCs Mostrecently Qiao and coworkers have exploited a novel fluo-rescent nanoprobe which contains fluorescent ovalbumin-cappedAuNCs biotarget folic acid and homopolymers as thelinker [72] Unlike most polymer-capped nanoclusters folicacid-functionalized fluorescent AuNCs can specificly labelthe cell and tumor which have superiority in biolabeling andbioimaging applications

(iv) DNA The introduction of biological macromolecules(protein DNA) can make the synthetic method of AuNCsgreener and more biocompatible which renders them morepossible for biological application Some reports have beenpublished to make the affinity of DNA base pair and AuNCsevident theoretically [73 74] which provide the foundationfor the subsequent experiments to verify the feasibilityof theories Chen and coworkers have unveiled atomicallymonodispersed AuNCs with direction of DNA as etchantof gold nanoparticles and rods [75] Liu and colleaguesfirstly reported that pH-dependent single-stranded DNA(ssDNA) was feasible in synthesizing blue-emitting AuNCswith a mild reductant [76] Shao and colleagues developeda nanoparticle-free method for synthesizing red-emittingAuNCs in water with DNA as a template [77]

(v) Small Molecules Most kinds of AuNCs are synthesizedby exploiting large templates such as dendrimers biolog-ical macromolecules (eg DNA proteins) and polymersMeanwhile small molecules used as the templates havebeen paid much attention for synthesizing high fluorescentAuNCs especially the thiol-protected (glutathione 11-mercap-toundecanoic acid) AuNCs [79] However using small mol-ecules as the templates and reductants has not drawn thatmuch attention for synthesizing high fluorescent AuNCscompared with other templates Several small molecules

UV light

Dispersion stabilityPhotochemical stabilityThermal stability

DMF-Au NCs Room light

(a) (b)

NO

H

N

O

H N

O

H

NOH

Figure 4 Schematic of DMF-AuNCs construction (a) the pho-tographs of DMF-protected Au clusters in DMF under ambient light(light yellow) and UV light of 365 nm (blue) (b) Reprinted withpermission from [78] copy2010 Langmuir

have been exploited in the fabrication of AuNCs such asamino acid [80ndash83] peptide [84 85] dimethylformamide[43 78] and Goodrsquos buffers [86] The report using aminoacid as a reactant for preparing AuNCs is scarce Chen andcoworkers [83] have discovered a fast facile method forpreparing AuNCs by blending Chloroauric Acid (HAuCl

4

)with histidine It is the first time for preparing AuNCs withamino acid as the reductant and stabilizer at the same timeKawasaki et al have reported the DMF-protected AuNCsthrough the interactions of the amide groups of DMF withAuNCs which possess high thermal stability high dispersionstability in various solvents and high photochemical stabilityas shown in Figure 4 [78]

222 Ligand-Protected Gold Nanoclusters Early studies forthe AuNCs are focused on synthesizing by strong reducingagent and strong capping agents such as thiol [87 88]dendrimers [34] and polymers [89] For synthesizing highyield of AuNCs a practical way was discovered involvingweaker reducing agent in the present of strong capping agentThis method can form nanoparticle-free AuNCs efficientlywith slower reduction rate [44] Due to excellent opticalelectronic and chemical properties ligand-protected goldnanoclusters have been extensively investigated especially fortheir potential applications in biomedicine andnanoelectron-ics

(1) Phosphine as Ligand [91] In the infant stage phosphinemolecules have been widely utilized as a ligand during thepreparation of AuNCs [92 93] The phosphine-cappedAuNCs are stable to the ambient conditions and controllableover cluster core size Generally phosphine-capped AuNCsare synthesized by sodium borohydride reduction Inthe 1960s an 11 gold atoms phosphine-protected clusterAu11

(PPh3

)7

(SCN)3

was firstly reported [92] And an Au13

-centered icosahedral structure cluster was successfully pre-pared in 1981 [94] Schmid et al reportedAu

55

-centered nano-clusters with an average core size ofsim14 nm [95]Themethodwas optimized by Hutchison and coworkers who developeda more convenient safer approach to synthesize phosphine-capped gold nanoclusters [96] In recent development ofphosphine-capped gold nanoclusters Wan et al isolatednew phosphine-protected Au

20

nanoclusters through thereduction of Au (PPhpy

2

) Cl [PPhpy2

= bis (2-pyridyl)phenylphosphine] by NaBH

4

the Au20

core was the fusion of


Glutathione (GSH)

in water

Au11 PPh3in chloroform

sim70mgAu25(SG)18

328K15h

Figure 5 Phosphine-stabilized Au11

clusters in chloroform were reacted with glutathione (GSH) in water under a nitrogen atmosphereReprinted with permission from [90] copy2005 American Chemical Society

two Au11

clusters [97] Although phosphine-capped AuNCsare one of the important classes in the gold clusters familiesthe synthetic method still faces some problems such astedious extractions numerous steps and unstable productiontending to decompose Since gold atoms have a good affinityto ndashSH groups the unstable phosphine-stabilized AuNCscould be transferred into thiolndashstabilized gold clustersHutchison and colleagues have reported a versatile ligand-exchange reaction and first described themechanismof thiol-phosphine ligand exchanges [98] As shown in Figure 5Shichibu et al synthesized glutathione-capped AuNCs (Au

25

(SG)18

) by ligand exchange with phosphine-stabilized Au11

clusters Teranishi and coworkers recently reported a bulksolution synthetic method that permitted large scale facilesynthesis of truly monodisperse Au

38

nanoclusters whichused a two-phase ligand exchange process based on GSH-Auclusters and led to monodisperse Au

38

nanoclusters in highpurity [90]

(2) Thiolate-Capped Gold Nanoclusters Brust et al have donethe pioneering work based on the reduction of the metalprecursors and the formation of metal core [99] Owing toa strong affinity for thiols and Au thiol-containing smallmolecules were extensively used to stabilize gold nanoclustersin the aqueous solution [6] Using thiol-containing smallmolecules as stabilizers rendered much more controllableAuNCs than phosphine-capped ones contributing to thestronger Au-S covalent bonding Thus they have beenintensely pursued in last decades

Generally the method of synthesizing thiolate-cappedAuNCs has processes as follows Gold salts [AuCl

4

]minus aredissolved in water and then transferred to an organic solventby phase transfer agent the thiols are added to the mixture toreduce Au3+ ions into Au+ ions and form Au+-SR complexesor polymers then the Au+ polymers are reduced by addingthe reducing agent into thiolate-protective gold nanoclusters

The fluorescence of thiolate-protected AuNCs (referredto as Au

119899

(SR)119898

where 119899 and 119898 are the respective numberof metal atoms and ligands) was effected by the kind ofligand and core charge state In order to enhance fluorescencedifferent chain lengths of thiols will be chosen for thebiolabeling and imaging applications [100] Jin and colleaguesdiscovered ldquosize focusingrdquo method to synthesize atomicallymonodisperse thiolate-stabilized AuNCs using different thiolligand (-SR -SC

2

H4

Ph -SC12

H25

SG and SC10

H22

COOH)[101]

Glutathione (GSH) a ubiquitous low-molecular weightthiol played a significant role in making AuNCs which

showed good water solubility bioactive surface and highstability It has been widely investigated for protecting theAu3+ ions when they were being reduced by sodium boro-hydride (NaBH

4

) [102ndash104] Whetten and coworkers haveunveiled an unprecedented thiol-protective AuNCs by usingthe GSH (N-120574-glutamyl-cysteinyl-glycine) as the stabilizerThe as-synthesized AuNCs were fractionated by using poly-acrylamide gel electrophoresis (PAGE) and characterized bymass spectrometry (MS) [102] Tsukuda and colleagues havealso reported the characterization of fractionated AuNCsprotected by GSHmonolayers using mass spectrometricTheas-preparedAuNCswere isolated into single-sizedAu

119899

(SR)119898

clusters by the PAGE method with 119899 = 18 21 25 28 32 39(called magic-numbered clusters) [103] Liu and coworkersemployed GSH-stabilized AuNCs (GSH-Au NCs) as the sen-sor of Cr (III) and Cr (VI) through fluorescence quenching[105] In the method GSH was used as an environmentfriendly reducingprotecting regent for preparing AuNCs inphysiological temperature for 24 h The as-prepared AuNCsexhibited yellow under visible light but the color turned intobright red when radiated by UV light as shown in Figure 6

Moreover various other thiols can be used to stabilize theAuNCs such as tiopronin [106] phenylethylthiolate [107] thi-olate 120572-Cyclodextrin [108 109] mercaptopropionic acid [110111] bidentate dihydrolipoic (DHLA) [112] dodecanethiol[113] and D-penicillamine [41 114 115] Using these mercap-tolinkers above makes the AuNCs possess higher fluorescentyield andmonodispersionMattoussi and coworkers [47] pre-pared a highly fluorescent gold nanoclusters with emissioncentered at sim750 nm NIR region using bidentate ligand asstabilizing agent Shang et al have reported a novel water-soluble Au-SR using the D-penicillamine (DPA) and a mildreductantTheDPA-capped AuNCs show an enhancement ofthe fluorescence intensity and a remarkable stability (simQY =13) which have potential for bioimaging application

23 ldquoNanoparticles to Clustersrdquo Route With the developmentof techniques a novel method is reported that involvesetching surface atoms of gold nanoparticles by appropriateligands Different small molecules and polymers have beenexploited as the etchant such as thiols (eg glutathionedihydrolipoic acid and phenylethylthiol) [16 116 117] andbiomacromolecules (eg BSA) Typical procedure containsthe following first mixing the surface-stabled gold nanopar-ticles with excessive etchant (small moleculespolymers) andthen etching the gold NPsrsquo surface via ligand exchangeand finally generating etchant-gold complexation Using thismethod can enhance the fluorescent effect of AuNCs (QYsim4ndash20)


(a)

300 400 500 600 700 800

Wavelength (nm)

Abso

rban

ce

Fluo

resc

ence

AbsorptionExcitationEmission

(b)

Figure 6 (a) GSH-protectedAuNCs under visible light (left) andUV light (right) respectively (b) UVvis absorption fluorescence excitation(emission at 710 nm) and emission (excitation at 410 nm) spectra of GSH-Au NCs Reprinted with permission from [105] copy2013 ScienceDirection

231 Ligand-Induced Etching In the past decades a series ofprotecting ligands have been exploited to prepare relativelycontrollable monolayer protected clusters (MPCs) The lig-ands such as phosphines thiols amines and polymers havemultiple functions in effecting the cluster size and physicalchemical properties Besides the one-pot method by directreduction of Au3+ ions in the presence of thiols mentionedabove fluorescent gold MPCs can be synthesized by etchingAu core with excessive ligands The study of monolayer goldMPCs has been separated into three stages polydispersednanoclusters monodispersed nanoclusters and atomicallyprecise nanoclusters [118] Jin et al have discovered a kinet-ically controlled method based on ligand-induced etchingfor preparing atomically monodisperse Au-SR called ldquosizefocusingrdquomethod For instance Jin and coworkers developeda facile high yielding synthetic approach to synthesize Au

38

(SC2

H4

Ph)24

clusters with excess phenylethylthiol Schaaffand coworkers conducted thiol etching on a combination of14k and 8k species the result showed that the 8 kDa speciesbecame enriched [119] Duan and colleague have reportedsynthesizing blue-emitting monodisperse AuNCs by exploit-ing the etching property of hyperbranched and multivalentpolymersmdashpolyethylenimine (PEI) In the approach as-prepared Au nanocrystals in dimension for sim8 nm weresynthesized bymodifiedBrust-SchiffrinmethodOnce actingwith excessive PEI the separated AuNCs with 8 atoms emit-ted intense green light under UV light irradiation (365 nm)as shown in Figure 7 [64]

Parak and coworkers reported a precursor-induced etch-ing method for the preparation of water-soluble fluores-cent dihydrolipoic acid-capped AuNCs [16] In the methodgold NPs stabled by didodecyldimethylammonium bromide(DDAB) were synthesized in the organic phase followed by

precursor induced etching into AuNCs Synthesis of water-soluble AuNCs was depending on the ligand exchange withreduced lipoic acid (DHLA) Upon the production transferto aqueous solution they became intensely red-luminescentwith QYsim345This report exhibited a totally novel methodfor preparing ultrasmall fluorescent AuNCs even if thedetailed mechanisms have not yet been clearly elucidated

232 Solvent-Induced Etching Phase transfer is demon-strated to be an effective approach for preparing the flu-orescent metal NCs via the electrostatic interaction Yuanet al [51] have developed a facile and versatile synthesis ofhighly fluorescent stable and monodispersed AuNCs basedon amild etching of originally polydispersed nonfluorescentand unstable gold nanocrystalsThiol-protected AuNCs weresynthesized by reducing the Au+-SR with the reducingagent (NaBH

4

) in the presence of glutathione (GSH) andthen transferring the polydispersed thiol-protected AuNCsinto an organic phase by adding cetyltrimethylammoniumbromide (CTAB) due to the electrostatic interactions betweennegatively charged carboxyl group in GSH and the positivelycharged cations of the hydrophobic salt [(CTA)+(COO)minus]The mild etching happened in the organic phase which ledto enhanced fluorescent monodisperse AuNCs Moreoverthe fluorescent AuNCs can easily be transferred back to theaqueous solution by injecting a salt to remove the (CTA)+This approach is used to fabricate highly fluorescent AuNCswith excellent stability biocompatible protecting ligands andmonodispersion which has a promising prospect in bioimag-ing and biosensing application Xie and coworkers have alsodiscovered a novel Au-thiolate NCs with highly lumines-cence (QYsim15) The mechanism of aggregation-inducedemission (AIE) has been discovered Due to the discovery


(a)

10

08

06

04

02

00

200 300 400 500 600 700 800

Wavelength (nm)

A(a

u)

(b)

(c) (d)

Figure 7 (a) and (c) are TEM of Au nanocrystals before and after ligand-induced etching (b) UV-vis spectra of the original Au nanocrystals(black) the etched nanocrystals after separation (red) the AuNCs mixture after etching (green) and the purified AuNCs after separation(blue) (d) Color photographs of the original Au nanocrystals in chloroform (left) and the purified AuNCs in water (right) UV light (365 nm)Reprinted with permission from [64] copy(2007) American Chemical Society

the nonfluorescent oligomeric Au (I)-thiolate complexes cangenerate strong luminescent under UV light depending onthe degree of aggregation The AIE properties can be usedfor designing AuNCs formed by the aggregation of Au (I)-thiolate complexes and in situ generated Au core whichaggregation was induced by adding a high concentration ofethanol in water as shown in Figure 8 [45]

3 Application of Gold NanoclustersBiosensing Biolabeling and Bioimaging

AuNCs as nanoprobes have several advantages as followsAuNCs have good stability and monodispersion in thephysiological environment leading to enhanced sensitivityand increased tracking lifetime AuNCs possess ultrasmallsize which can be easily uptaken by cells the biologicalfunctions of bioentities conjugated with AuNCs will not bedisturbed photoluminescence in the form of fluorescence isan important property of AuNCs with decreasing the coresize their fluorescence will show a blue-shift from the NIRregion to ultraviolet the QY of AuNCs is much higher than

bulk gold and gold NPs in magnitude compared with theharsh synthetic steps and tedious surface modification ofquantum dots it is much more achievable to prepare AuNCsand the functional groups induced by the templates andstabilizers are much convenient for coupling with the dyespeptide DNA and othermarkers owing to the low content ofmetal AuNCs have good biocompatibility for lots of in vitroand in vivo applications

As mentioned above fluorescent AuNCs are promisingmaterial as fluorescent biolabels and light-emitting sourcesin nanoscale therefore they can be applied in biologicallabeling imaging detection and so on

The precondition for making the applications possible isappropriate surfacemodification forAuNCs which can even-tually influence their stability biocompatibility targetingand other properties The method functionalizing AuNCsinvolves surface chemistry and bioconjugation which shouldpromise AuNCs survival in these conditions Herein we willsummarize the strategies which are widespread in synthe-sizing functional AuNCs as fluorescent biological probes inbiolabeling bioimaging and biosensing applications


Aqueous

AuSR

Ethanol Ethanol

H2O H2O

Denseaggregates

Highly emissiveLoose

aggregatesWeakly emissive

Oligomericcomplexes

Nonemissive

75 ethanol

95 ethanolh

h

[ ]n

(a)

fe 0 30 60 65 70 75 80 85 90 95()

(b)

Abso

rban

ce (a

u)

Wavelength (nm)200 400 600 800

95

90

85

80

75

70

65

60

30

0

(c)

PL in

tens

ity (a

u)

PL in

ten

(au

)

0 20 40 60 80 100fe (vol)

70

65

60

30

0

95

90

85

80

75


(d)

Figure 8 (a) Schematic illustration of solvent-induced AIE properties of oligomeric Au (I)-thiolate complexes (b) Digital photos of Au (I)-thiolate complexes in mixed solvents of ethanol and water with different 119891

119890

under visible (top row) and UV (bottom row) light (c) UV-visabsorption and (d) photoemission spectra of Au (I)-thiolate complexes in mixed solvents with different 119891

119890

(Inset) Relationship between theluminescence intensity and119891

119890

The spectra were recorded 30min after the sample preparation Reprinted with permission from [45] copy(2012)American Chemical Society

31 Surface Functionalization Nanoparticles are usuallymodified with a variety of materials such as silica syntheticpolymers biopolymers dendrimers and small moleculesleading to introducing desired functionality [120 121] In theearly days surface modification is based on chemisorptionthrough which bonds are weak and easy to rupture Anovel strategy offering a stronger and more robust bond hasbeen discovered to modify NPs with more stable ligands[122] which make it possible for AuNCs holding promisingapplications in the biological field in vitro and in vivo Hencethere are several demands toAuNCs (1) they should bewater-soluble and stable in a physiological environment (2) theyshould possess targeting to specific tissuewith high selectivityin vivo and (3) they should be efficiently discharged by themetabolic system for lowest toxicity [121] In order to fit thebills a mountain of work has been done to tailor functionalAuNCs with various coating and bioconjugation

The silica coating one of the most multifunctional meth-ods of surface functionalization can couple the advantage ofBSA-templated AuNCs with the silica particles Guevel andcoworkers [123] have highlighted a novel kind of fluorescent

core-shell nanoparticles by BSA-templated AuNCs The as-prepared AuNCs doped Si NPs showmonodispersion higherstability NIR emissionwavelength and enhanced fluorescentintensity Moreover the silica shell allows AuNCs to beconjugated with bioactive entities (eg peptide folic acid(FA) antibody and polymer)

Bioconjugation is an effective route to introduce extrafunctionality onto nanoclusters through several functionalgroups such as primary amide carboxylic acid alcoholsand thiols [124] According to the synthesis of AuNCs aswe have discussed before the majority of template-directedand ligand-protected clusters possess the carboxylic acids onthe surface as functional groups which can conjugate withamino-terminal biomolecules The reaction is commonlycatalyzed with 1-ethyl-3-(3-dimethylaminopropyl) carbodi-imide (EDC) and sulfo-N-hydroxysuccinimide (sulfo-NHS)to form amide bond Yan and colleagues have developedan approach to conjugate Cyclo(Arg-Gly-Asp-D-Phe-Lys)(RGD) peptide to BSA-stabilized AuNCs with the use of cou-pling agents [125] A simple one-potmethod has been studiedby Shang and colleagues for synthesizing D-penicillamine-capped AuNCs which have both amino and carboxylic


groups on the surface for further bioconjugation Abadand coworkers have synthesized AuNCs capped with dihy-drolipoic acid (DHLA) which possess hydrophilic carboxylgroup providing an anchor for biological molecules conju-gation such as covalent linkage [126] AuNCs coated withcarboxylic acid have been bonded with polymers containingamine functionalities by ion pairing without EDC and NHSMattoussi and coworkers have reported preparing theAuNCsstabilized with zwitterion-appended lipoic acid ligands inwhich process reactive groups (amine or carboxyl group) canbe inserted in situ on the surface of production for furtherbioconjugation [47]

In addition to the further steps for surface function-alization the introduction of ultrabiocompatible interfaceand the protection of AuNCs have occurred simultaneouslyin terms of the template-directed fluorescent AuNCs Forinstant proteins such as BSA are extensively exploited asthe stabilizers for preparing fluorescent AuNCs bringing incontrollable functional groups [127 128]

32 Biological Sensing Application The minitype sensor innanoscale is of interest in the wide array of biomedicalapplications and environmental science for detection ofmetalions and biomolecules possessing high sensitivity and lowcost The surface modified AuNCs can be utilized as biosen-sors with the fluorescent AuNCs core as transducer and thesurface functionalized molecules as recognition component

321 Heavy Metal Ions Detection Due to high hazard andbioaccumulation in vital organs and tissues of heavy metalions such as mercury copper and chromium ions relatedinvestigations of heavy metal ions detection have receivedincreasing attention For the sake of protecting our environ-ment and health some effective strategies are highly desirablefor the sensitive and selective detection of heavy metal ions

The detection of Hg2+ is based on biomolecules (proteins[129 130] antibodies [131] oligonucleotides [132] DNAzyme[133 134] etc) gold nanoparticles [135 136] small organicmolecules [137 138] and other materials such as inorganicmolecules [139 140] Recently AuNCs have been exploitedas the sensor of Hg2+ Xie et al initially developed amethod to synthesize AuNCs with BSA and further apply theBSA-templated AuNCs to the Hg2+ sensing in 2010 [141]This approach utilized the specific and strong interactionbetween the Au+ and Hg2+ which effectively quenched thefluorescence of AuNCs This process can specifically detectand monitor Hg2+ ions at minimal concentration of 05 nMTseng and Lin have reported selectively sensing Hg2+ andCH3

Hg+ using lysozyme type VI-stabilized AuNCs (Lys VI-AuNCs) through the interaction between Hg2+CH

3

Hg+ andAu+ on the cluster surface as shown in Figure 9 The limitof detection (LOD) for Hg2+CH

3

Hg+ was 3 pM and 4 nMrespectively [54] which is much lower than the maximumconcentration in the drinking water permitted by the USEnvironmental Protection Agency (EPA)

Chang and colleagues have unveiled a new assay for thehighly selective and sensitive detection of Hg2+ ions basedon aggregation-induced quenching of the fluorescence of 11-mercaptoundecanoic acid (11-MUA) protected AuNCs This

Li+

Na+ K+

Mg2

+

Ca2+

Ba2+

Fe2+

Fe2+

Co2

+

Ni2+

Cu2+

Zn2+

Mn2

+

Ag+

Cd2

+

Pb2+

Cr3+

CH3H

g+

Hg2

+

CH3H

g++

Hg2

+

0

01

02

Sr2+

(IF0minusI F

)I F

0

(a)

0

01

02

F∙ Cl∙

Br∙

Citr

ate3

∙Ac

O∙I∙

(IF0minusI F

)I F

0

ClO4∙

BrO

3∙

IO3∙

NO

2∙

NO

3∙

CO32∙

HCO

3∙

SO32∙

SO42∙

S 2O32∙

PO42∙

HPO

42∙

H2P

O4∙

BO33∙

(b)

Figure 9 Relative fluorescence intensities [(1198681198650

minus 119868119865

)1198681198650

] at 631 nmof solutions of Lys VI-AuNCs after the addition of (a) Hg2+(100 nM) CH

3

Hg+ (100 nM) and other metal ions (50120583M) and (b)anions (50120583M) The excitation wavelength was set to 400 nm Theincubation time was 10min It should be noted that 119868

1198650

and 119868119865

arethe fluorescence intensities of the AuNCs before and after addinganalytes respectively Reprinted with permission from [54] copy2010Analytical Chemistry

fluorescence quenching induced by the aggregation of goldNPs in the present of Hg2+ was firstly reported as a methodfor sensing metal ions [33]

Copper widely exists and is essential for all the plantsand animals for being the key factor in producing numerousenzymes and involved in various physiologic processeshowever excessive copper ions will lead to cellular toxicityliver damage and other damages of organisms [54 142 143]Thus considerable efforts have beenmade in the field of Cu2+detection using fluorescent AuNCs as a sensor Gaetke andcolleagues have demonstrated a novel method using GSH-stabilized AuNCs as highly sensitive and selective fluorescentsensor for copper ions based on ion-induced aggregationof AuNCs [144] In addition the quenched fluorescence ofAuNCs can be recovered through adding a strong metalion chelator ethylenediaminetetraacetate (EDTA) Guo andcoworkers also reported a novel synthetic approach of NIRfluorescent AuNCs recently which was realized by the heat-assisted reduction of an Au+-thiol complex The as-preparedAuNCs are able to selectively and sensitively detect copper


h998400 h998400

h h

H2O2

HRP-AuNCsHRP

(a)

0

100nM250nM500nM1120583M5120583M10120583M25120583M50120583M100120583M

400 450 500 550 600 650 700

0

50

100

150

200

250

300

350

FL in

tens

ity (a

u) 35

40

45

50

55

01 05 1 5 10

I 450l 4

50

120582 (nm)

[H2O2] (120583M)

(b)

Figure 10 Schematic of the formation and the H2

O2

directed quenching of HRP-AuNCs Reprinted with permission from [127] copy2011American Chemical Society

ions with a minimal concentration as low as 16 nM [145]Guo and coworkers published the detection method of Cu2+employing lysine-functionalized AuNCs (AuNCsLys) asfluorescent probes [146] The mechanism of this sensingprocess is the tunable fluorescent signal of AuNCsLysquenched by the link of copper ions and lysine The concen-trate scale the probe can determine is from 10 nM to 7 120583Mwhich is far low than the maximum level of Cu in drinkingwater (20120583M) permitted by the EPA of the US [147]A masking method for improving selectivity of AuNCs hasbeen developed by Cao and coworkers for higher selectivedetection of mercury and copper ions By adding the ldquomask-ingrdquo agents respectively Cu2+ and Hg2+ ions are inhibitedto interact with AuNCs and eliminated the correspondingquenching effect thus the ions without being inhibited canbe detected [148]

Moreover Ho and coworkers have described a facile one-pot method to sense ferric ions by the fluorescent AuNCsstabilized and reduced by L-3 4-dihydroxyphenylalanine(L-DOPA) The as-prepared AuNCs exhibited a fluorescentquench based on the ferric ions-induced aggregation whosedetection limit of the Fe3+ was lower than themaximum levelallowed by the US EPA (54 120583M) [149]

322 Small Molecules and Biomacromolecules Detection Inaddition to heavy metal ion detection fluorescent AuNCscan also be exploited detecting small molecules (hydrogenperoxide [40 150] enzymes [151ndash153] dopamine [154ndash156]nitrite [157] cholesterol [158] folic acid [159] ciprofloxacin[160] etc) and biological macromolecules (proteins [161ndash166] glucose [40 167] etc) Zhang and coworkers haveshowed a biomineralization strategy for the detection ofhydrogen peroxide by synthesizing the AuNCs by a func-tional templatendashHorseradish peroxidase (HRP) at physio-logical conditions [127] The fluorescence of HRP-stabilized

AuNCswas quenched upon the addition ofH2

O2

in the rangefrom 100 nM to 100 120583M with a LOD of 30 nM as shown inFigure 10

The detection of biological thiols such as cysteine (Cys)and glutathione (GSH) has been extensively investigatedCys plays an important role in biological system from theprotein formation to being an antidote for alcoholic adversereactions GSH is the most abundant thiol in cells whichparticipates in numerous biological reactions such as neu-tralizing free radicals and peroxides HIV expression andcancer therapy which show that the altering level of GSH isrelated to the diabetes andHIV disease So the level of GSH inbiological organism is measured with great importance Parkand coworkers have elaborated the detection of biologicalthiols systematically by using the BSA-stabilized AuNCsThemethod is based on Hg2+-induced fluorescence quenchingthrough high affinity of Au+ and Hg2+ and blocking thisinteraction by selective coordination of thiols with Hg2+This fluorescence-based sensing method for biothiols hasadvantages such as simple steps fast reaction time and cost-effectiveness Recently Huang et al have reported a simpleimmune-dependent and label-free method for cystatin C(Cys C) detection To achieve the detection BSA-templatedAuNCs have been employed as the fluorescent probe whichprocess is based on the papain-induced quenching of AuNCsand the fluorescent recovery by the coexistence of CysC Papain can digest the scaffold of AuNCs BSA basedon its protease activity and Cys C as a powerful cysteineproteinase inhibitors capable of inhibiting the activity ofpapain to protect the AuNCs from aggregation FluorescentAuNCs enable detecting Cys C in the range of 25 ngmLndash20 120583gmL Tseng et al have also presented a method forsensing glutathione (GSH) by (Lysozyme Type VI) stabilized(Lys VI) AuNCs (contain 8 gold atoms) The PH-dependent


blue-emitting AuNCs could detect GSH resulted from theformation of GSH-Au+ complexes By specific etching reac-tion of GSH and AuNCs core the fluorescence of AuNCs wasquenched to show the altering level of GSH with a sensinglimitation of 20 nM

Dopamine (DA) as a vital catecholamine neurotrans-mitter plays a significant role in the central nervous renaland hormonal systems [168] The detection of DA withsimple high performance nontoxicity has been developedemploying the AuNCs as biosensor Qu and coworkershave firstly discussed the detection of dopamine involvingBSA-templated AuNCs electrogenerated chemiluminescence(ECL) study [155] The process was realized by injectingDA into the electrolyte the ECL of the AuNCs exhibiteda distinct linear increase response to the increase of DArsquosconcentrationThe highly sensitive and selective fluorescenceand colorimetric sensing ofDAwas in the first time describedusing a BSA-stabilized AuNCs by Sony and colleague [154]The fluorescence of BSA-AuNCs showed a decrease onceadding DA due to the photoinduced electron transfer of DAto AuNCs In the meantime the peroxidase-like activity ofAuNCs was inhibited in the present of DA leading to a visualdetection with highly selectivity

AuNCs-based fluorescent protein sensor can be achievedby coupled selective recognition molecules with the fluores-cent AuNCs Of the substantial trial for forming AuNCs-based protein sensors Leblancrsquos group initially reported theconjugation of anti-human IgG to the PAMAM-stabilizedAuNCs for detecting the human IgG antigen [161] Linearfluorescence quenching coordinated with the formation ofantigen-antibody immunocomplexes Chang and colleaguesunveiled a novel protein sensor by using the light switchingsystem based on biofunctional 11-MUA-protected AuNCsand bioconjugated 13 nm gold NPs [165] Platelet-derivedgrowth factor AA (PDGF AA) as a breast cancer markerprotein can be conjugated to AuNCs (PDGF AA- AA-LAuND) Thiol-derivation aptamers (Apt) with high affinity toPDGFs interacted with gold NPs (Apt-QAuNP) PDGF AA-LAuND can attach to theApt-QAuNP leading to the fluorescencequenching by resonance energy transfer Upon the additionof free PDGF or PDGF 120572-receptor the fluorescence can berecovered as a result of competitive reaction of PDGFApt-QAuNP or PDGF 120572-receptorPDGF AA-LAuND as shown inFigure 11 The mannose-protected AuNCs have also beensynthesized for the detection of Concanavalin A (Con A)with high sensitivity and other proteins and lectins [166]In this method the fluorescent AuNCs were synthesizedby etching the THPC-reduced AuNCs by excessive Man-SH which showed a high sensing limitation to Con A andE coli attributed to multivalent cooperative interactionsbetween Man-AuNCs and proteins This approach providedthe lowest LOD value for Con A (75 pM) and yielded brightlyfluorescent cell clusters when binding to bacteria

Glucose on one hand is the major energy source ofliving cells of significance in the synthesis of other complexmolecules and an important factor of human health con-dition on the other hand it leads to many diseases suchas diabetes when holding at an abnormal level Typicallythe detection of glucose by the fluorescent AuNCs probes is

Apt-Q AuNP

Apt-QAuNPPDGFs

Apt-QAuNP

PDGF receptor

FRET

FRET

FRET

h 998400h

h 998400h

h 998400h

PDGF receptor

(a)

(b)

(c)

AuNDPDGF AA-L

AuNPApt-Q

Figure 11 Schematic representations of PDGF and PDGF recep-tor biological nanosensors blocking the fluorescence quenchingbetween PDGF AA-LAuND and Apt-QAuNP Reprinted with permis-sion from [165] copy(2008) American Chemical Society

as follows the biomolecules-stabilized AuNCs were synthe-sizedmoreover glucose can be oxidized by oxygen incubatedwith glucose oxidase (GOD) which produces H

2

O2

as theintermediation The H

2

O2

-induced aggregation of AuNCscan lead to the fluorescence quenching and vicariouslydetecting the glucose [168 169]

33 Biological Labeling and Imaging AuNCs as an emergingfluorescent nanomaterial possess a dramatic number of char-acteristics as follows ultrasmall size good water solubilitybiocompatibility photostability and large Stokes shifts allthese properties make them promising fluorescent probes forbiological labeling and imaging [170 171]

The fluorescent AuNCs as cell labels are considered torealize the long observation times and stable emission offluorescence microscopy in live cells so as to understand thedynamics of intracellular networks better Parak et al haveprepared water-soluble fluorescent DHLA-protected AuNCs(AuNCsDHLA) then bioconjugated with streptavidin forspecific probing of the intracellular distribution of endoge-nous biotin in liver cell [16] Thereafter an investigationwas also described by Chang and coworkers to elucidatethe fluorescent and biocompatibility features of AuNCs bylabeling the endothelial progenitor cells (EPC) [172] Theresult indicated that the fluorescence of labeled cells did notdecrease as well as maintained intact angiogenic potential


ApoptosisCyt C

Cellular uptake

Endosome

GSHEndosomeescapeNucleus

Mitochondria

Figure 12 Intracellular GSH-triggered release of anticancer drugsloaded within DEGNPs Reprinted with permission from [178]copy2013 American Chemical Society

Furthermore AuNCs are attractive in the biomedicinefield for diagnostics and therapeutics due to ultrasmallsize strong fluorescence emission and good biocompatibility[172ndash176] Irudayaraj and coworkers have described the flu-orescent BSA-protected AuNCs conjugated with Herceptin(AuNCs-Her) for targeting fluorescent imaging and cancertherapy at the same time [177]The ultrafine novel fluorescentprobes were demonstrated having the ability to enter thenucleus with high targeting specificity and nuclear localiza-tion capability for effective drug delivery and therapeuticefficacy Botella and coworkers have designed a photother-anostic agent based on chlorin e6 (Ce6) photosensitizer-conjugated silica-coated AuNCs (AuNCSiO

2

-Ce6) for flu-orescent imaging-guided photodynamic therapy [175] Andmost recently Cheng and colleagues have published the firstreport of using Dendrimer-encapsulated gold nanoparticles(DEGNPs) as the scaffold to develop stimuli-responsive drugdelivery systems as shown in Figure 12 [178] The DEGNPscan be loaded with thiolates anticancer drugs via Au-S bondAfter triggering to the tumor cell by GSH the drugs can bereleased in tumors This strategy opened up new possibilitiesto exploit subnanosized NPs for an ldquooff-onrdquo drug releasesystem

In addition to achieve more effective therapeutic effectAuNCs-based probes can also be utilized for highly specificand accurate cancer diagnosis Most recently to achieve highaccuracy and specificity of cancer diagnosis novel fluores-cence enzyme mimetic nanoprobes have been described byChen et al based on folic acid modified gold nanoclusters[173] In this method the BSA-stabilized AuNCs were syn-thesized to facilitate a rapid cost-effective and versatile NIRimagingvisualizing cancer diagnosis systemThe peroxidasemimetic AuNCs conjugated to folic acid possess enhancedtargeting ability to folate receptor over-expressing tumorsand combined with other superior properties they canbe employed for a colocalization staining method whichdiagnoses cancer rapidly through microscopic imaging withbright field and fluorescent imaging simultaneously

Biological imaging in vivo is confronted with much morechallenges than cellular imaging such as difficulty in survivein complex physiological environment and weak intensityof visible light blocking by organic tissue The emitted light

in the NIR region of AuNCs is capable of penetrating intodeeper tissue and detecting stronger intensity due to weakestbiological autofluorescence Besides unlike the toxic QDsand low-stability organic dyes AuNCs with ultrafine sizegood water-solubility biocompatibility and good photosta-bility are of great interest to be fluorescent nanoprobes forbiological imaging As mentioned above AuNCs are idealbioprobes for bioimaging in vivo Herein we will show thelatest development in bioimaging

The two-photon excitation photoluminescence measure-ment was utilized to demonstrate the strong advantage in livecell imaging compared with organic dyes and quantum dotssuch as the ability of deeper inside tissues and the reducedphototoxicity of NIR light Goodson and colleagues haveinvestigated two-photo absorption (TPA) of Au

25

clustersin NIR region in organic phase and TPA cross-sectionsincrease to an extremely high level at 800 nm which makeit possible for applications in optical power limiting nano-lithography [182] Xu and coworkers have investigated theone- and two-photon excitation properties of water-solubleGSH-protected AuNCs and their applications in bioimaging[183] In this report the TPA property and application asfluorescence imaging contrast agents of GSH-AuNCs havebeen explored The TPA cross section of GSH-AuNCs ismuch larger compared with organic dyes and QDs as wellas the low toxicity and exceptional photostability whichshow their as promising in live cell fluorescent imagingand other bioimaging in vivo Shang et al have studied theprocess that DPA-AuNCs are internalized by HeLa cells inendosomal vesicles through two-photo imaging [41] After2 hours of incubation of DPA-AuNCs and HeLa cells theimages were captured by confocal microscopy with two-photon excitation The fluorescence of probes ingested bythe HeLa cells can easily be seen through 3D reconstructionimages which reveal the nanoclusters inside the cells as wellas those attached to the outside of the plasma membraneThe study of two-photon induced luminescence of 11-MUA-AuNCs has been reported by Chou and co-workers Thetwo-photon induced fluorescent imaging was used to humanmesenchymal stem cells (hMSCs) through the stable andnontoxicity nanoprobes which revealed that the 11-MUA-AuNCs were internalized into the cells and mainly resided inthe cytoplasmnearby the nucleus as shown in Figure 13 [179]

Comparedwith fluorescent intensity imaging fluorescentlifetime imaging microscopy (FLIM) could separate thespecies based on differences in the exponential decay rateof fluorescence (lifetime) which is independent of the localconcentration of fluorescent molecules and the excitationintensity [184] Shang and colleagues have investigated thefluorescent DHLA-AuNCs in HeLa cells by the FLIM tech-nique The lifetimes of DHLA-AuNCs (gt100 ns) is two orderofmagnitude longer than the lifetime of biological fluorescentfluorophores Owing to this the biological imaging can beachieved in the complete absence of cellular autofluorescenceThe intensity and lifetime images of cell without and withAuNCs have been shown and indicated that the AuNCshave been internalized by the cells The as-prepared NCshave many other features for promising candidate of wideapplications in biomedical field In the meantime Irudayaraj


50120583m

(a)

50120583m

(b)

50120583m

(c)

50120583m

(d)

Figure 13 hMSCs were treated with dextran-coated 11MUA-Au nanodots for 24 h and then processed for two-photon and confocalmicroscopic examination (a) Cell nucleus was stained with DAPI (blue color) (b) Actin fiber was stained with rhodamine phalloidin toconfirm the cell boundary (red color) (c) Dextran-coated 11MUA-Au nanodots exhibit a two-photon emission (green luminescence) for invitro bioapplication (d) Fluorescence image overlay of the three images demonstrating the internalization of 11MUA-Au nanodots residingnear the nucleus Reprinted with permission from [179] copy2009 American Chemical Society

and workmates have exploited FLIM combined with fluores-cent correlation spectroscopy (FCS) to track the diffusion ofHerceptin-conjugated AuNCs and its entry into the nucleusin SK-BR3 cells [177] The SK-BR3 cell is a human breastcancer cell overexpressing human epidermal growth factorreceptor 2 (HER2) on the cell membrane The AuNCs-Herwas specifically endocytosed into the nucleus of SK-BR3cells causing DNA damage showed by FLIM as shown inFigure 14

Biological imaging in vivo is confronted with much morechallenges than cellular imaging such as difficulty in survivein complex physiological environment and weak intensityof visible light blocking by organic tissue The emitted lightin the NIR region of AuNCs is capable of penetrating intodeeper tissue and detecting stronger intensity due to weakestbiological autofluorescence Besides unlike the toxic QDsand low-stability organic dyes AuNCs with ultrafine sizegood water-solubility biocompatibility and good photosta-bility are of great interest to be fluorescent nanoprobes forbiological imaging All of these properties indicates thatAuNCs are ideal bioprobes for bioimaging in vivo Herein wewill show the latest development in bioimaging

Zhang et al have developed the utilization of AuNCsintomultimodal imaging technique for early cancer diagnosis

[185] In this method BSA-stabilized AuNCs are synthe-sized as the highly fluorescent and strong X-ray absorptioncoefficient contrast agent for fluorescent and X-ray dual-modality imaging Coincidentally Cui and coworkers haveprepared FA-conjugated AuNCsSiO

2

nanoprobes for invivo dual-modal fluorescent and X-ray computed tomogra-phy gastric cancer targeting imaging [180] Nude mice modelwith xenograft tumor based on MGC-803 cells was injectedwith these targeting fluorescent nanoprobes via tail veinfollowed by dual-modal imaging The experimental resultsdemonstrated that FA-conjugated AuNCsSiO

2

can effec-tively target in vivo gastric cancer cells and exhibited excellentNIR fluorescent imaging and presented distinguished CTsignals in X-ray imaging as shown in Figure 15

Moreover a multimodal imaging method blending NIRfluorescent imaging and magnetic resonance imaging (MRI)has been achieved by Koyakutty and coworkers recently withthe aid of gadolinium oxide and Au (Gd

2

O3

Au) hybridtargeting nanoprobes [186] The as-synthesized nanoclustersfabricated by biomineralization showed both intense red-emitting fluorescence and good magnetic resonance imagingability and were further functionalized with RGD peptidefor realizing the targeted tumor imaging application in vivoIn addition the over expression of 120572

119881

1205733

integrin in U87


(a)

(b)

(d)

(e)

(c)

DN

A d

amag

e rat

e

0

20

40

60

80

100

Herceptin AuNCs-Herceptin AuNCs

(f)

Figure 14 Fluorescent images showed the cell apoptosis induced by (a) AuNCs alone (b) AuNCs-Her (c) Herceptin by staining the nucleuswithHoechst 33258 (UV light 460 nm) FLIM shows the DNA damage of SK-BR3 cells induced by (d) AuNCs-Her (e) Herceptin indicated bythe bright yellow dots (f) Quantitative evaluation of DNA damage of cells as a percentage of the total number of cells for different treatmentsReprinted with permission from [177] copy2011 American Chemical Society

tumor cell can enhance the specific accumulation of RGD-Gd2

O3

Au RGD conjugated Gd2

O3

Au (RGD-Gd2

O3

Au)nanoclusters injected into U87-MG tumor-bearing mice viatail vein showed distinguished specific accumulation in U87tumor with longer retain time for targeted bioimaging invivo Currently the majority of nanoprobes conjugated totargetable molecules are synthesized in labs followed by thepurify steps and then injected into live animals Althoughpossessing ultrasmall size (nanoscale) relative stability inbiological systems and validated biocompatibility the exoge-nous nanoprobes will reach the specific site through organic

circulation which inevitably triggers the clearance effect ofbiosystems In order to overcome this problem Wang andcompanions have created a biosynthesize method of AuNCsinside the cytoplasm through enforcing an efficient sponta-neous reduction of chloroauric acid biocompatible salts bycancer cells as shown in Figure 16 [181] Although the mech-anism of this novel bioimaging of cancer cells and tumors isstill unknown AuNCs have been successfully formed insidethe cytoplasm and confirmed in vivo for specially labeling onthe xenograft tumor mouse modal by fluorescent imagingThus this novelmethod is remarkable not only for facilitating


28mgmL 56mgmL 112mgmL 224mgmL

5000

19500

33000

46500

60000

(a)

25000

37500

50000

62500

75000

(b)

45250

59922

74588

89254

(c)

Figure 15 AuNCsSiO2

-FA nanoprobes for fluorescence imaging (a) In vitro fluorescence image of AuNCsSiO2

-FA in 001M PBS withdifferent concentrations (b) In vivo fluorescence image of 50 uL AuNCsSiO

2

-FA injected subcutaneously at three different doses (area-156mgmL area-2 112mgmL area-3 226mgmL) into the left mice The left mice without injection was selected as control (c) fluorescenceimage of tumor tissues with tail vein injection at the concentration of 287mgmL at 6 h postinjection Reprinted with permission from [180]copy2013 Journal of Nanobiotechnology

fluorescent nanoprobes with biosynthetic self-imaging andNPs circulation elusion peculiarities but also for showing adifferent concept of highly sensitive and specific nanoprobesfor bioimaging application compared with current system

4 Summary and Outlook

Fluorescent AuNCs as an emerging fluorescent nanoma-terial possess a great deal of exceptional advantages suchas good water-solubility high photostability large Stokesshift ultrasmall size nontoxicity and good biocompatibilitycompared with conventional organic dyes rare earth-basedquantum dots and other luminescent materials Herein firstof all we have briefly summarized various approaches thathave been employed for preparing AuNCs based on tworoutes ldquobottom-uprdquo and ldquotop-downrdquo routes Recent advancesof the development of the synthetic methods have a far-reaching influence on the future functionalization of AuNCsThe surface modification of AuNCs endows a number ofnew functionalities for them like targeting imaging propertiesand therapeutic effects In the second part the most recentadvances of bioapplications have been summed up such as

fluorescent detection of metal ionsbiomolecules fluorescentcell labeling and bioimaging in live animal

Although a huge progression has been achieved todevelop the promising novel fluorescent nanoprobes a vari-ety of challenges in the way still make the future progress ofAuNCs

With regard to the synthesismethod and physical proper-ties there are several challenges we need to face in the futurestudy Even with making tremendous efforts to optimizethe synthetic routes problems remain existent such as theunpurified AuNCs being polydispersed in the solvent andexhibiting quantum yield lower than 20 within a broademission band What is more there is scarce strategy forpreparing size-focusing AuNCs with high reactive yield andmonodisperse advantage Finally the relationship betweenthe structure and optical properties ofAuNCs requires deeperinvestigation

For the application of AuNCs most of biological applica-tions focus on employing them as biosensors or fluorescentnanoprobes in bioimaging and more applications involvedin the therapy of tumor can be developed Furthermorethe interaction between biological environment and AuNCs


Fluorescent imaging

Incubation for

24h or 48h

Complex ofbiomolecule andgold-nanocluster

HAuCl4

h

Gold-nanocluster

Tumor

(a)

Scal

ed (c

ount

ss)

0

001(b) (c) (d)

Figure 16 Schematic illustration of in situ biosynthesis of gold nanoclusters in cells and tumor imaging (top) Representative xenograft tumormouse models of hepatocellular carcinoma observed in normal light (a) or by in vivo fluorescence imaging (b) 24 h after a subcutaneousinjection of 10mmolL HAuCl

4

solution near the tumor (c) 24 h after a subcutaneous injection of 10mmolL HAuCl4

solution near thetumor (d) Control mouse observed by in vivo fluorescence imaging 48 h after a subcutaneous injection of 10mmolL HAuCl

4

solution inthe right side of their abdomen (bottom) Reprinted from the permission of [181] Copyright copy2013 Rights Managed by Nature PublishingGroup

is significant for the biological application of nanoprobeshowever most investigators judge the performance in organ-ism centering in the matter of nanomaterial themselves(photostability size-depending properties etc) but ignoringthe interaction between the organism and AuNCs which isrelated to the safety of AuNCs used in the bionanotechnologyand the mechanism of biological applications

In a word gold nanoclusters with fascinating propertieshave been extensively investigated and achieved markedadvance Nevertheless the application of AuNCs in biologicalfields is still in the preliminary stage and large amounts ofstudy are waiting for us in the synthesis comprehending ofinteractionmechanismmaking full use of the decent featuresof AuNCs and extending the range of biological applications

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgments

This work is supported by the Program of the National BasicResearch and Development Program of China (973) underGrant no 2011CB707702 and the National Natural ScienceFoundation of China under Grant nos 81371589 81090272and 81101084 and the Fundamental Research Funds for theCentral Universities

References

[1] E C Dreaden A M Alkilany X Huang C J Murphyand M A El-Sayed ldquoThe golden age gold nanoparticles forbiomedicinerdquo Chemical Society Reviews vol 41 no 7 pp 2740ndash2779 2012

[2] M C Roco ldquoNanotechnology convergence with modern biol-ogy and medicinerdquo Current Opinion in Biotechnology vol 14no 3 pp 337ndash346 2003


[3] L Shang S Dong andG U Nienhaus ldquoUltra-small fluorescentmetal nanoclusters synthesis and biological applicationsrdquoNanoToday vol 6 no 4 pp 401ndash418 2011

[4] M-C Daniel and D Astruc ldquoGold nanoparticles assemblysupramolecular chemistry quantum-size-related propertiesand applications toward biology catalysis and nanotechnol-ogyrdquo Chemical Reviews vol 104 no 1 pp 293ndash346 2004

[5] Z Wu and R Jin ldquoOn the ligandrsquos role in the fluorescence ofgold nanoclustersrdquo Nano Letters vol 10 no 7 pp 2568ndash25732010

[6] R Jin ldquoQuantum sized thiolate-protected gold nanoclustersrdquoNanoscale vol 2 no 3 pp 343ndash362 2010

[7] Q Zhang J Xie Y Yu and J Y Lee ldquoMonodispersity controlin the synthesis of monometallic and bimetallic quasi-sphericalgold and silver nanoparticlesrdquoNanoscale vol 2 no 10 pp 1962ndash1975 2010

[8] L Zhang and E Wang ldquoMetal nanoclusters new fluorescentprobes for sensors and bioimagingrdquo Nano Today vol 9 no 1pp 132ndash157 2014

[9] J Zheng C W Zhang and R M Dickson ldquoHighly fluorescentwater-soluble size-tunable gold quantumdotsrdquo Physical ReviewLetters vol 93 no 7 2004

[10] S W Chen R S Ingram M J Hostetler et al ldquoGold nano-electrodes of varied size transition to molecule-like chargingrdquoScience vol 280 no 5372 pp 2098ndash2101 1998

[11] J F Hicks A C Templeton S Chen et al ldquoThe monolayerthickness dependence of quantized double-layer capacitances ofmonolayer-protected gold clustersrdquo Analytical Chemistry vol71 no 17 pp 3703ndash3711 1999

[12] J F Hicks D T Miles and R W Murray ldquoQuantized double-layer charging of highly monodisperse metal nanoparticlesrdquoJournal of the American Chemical Society vol 124 no 44 pp13322ndash13328 2002

[13] BMQuinn P LiljerothV Ruiz T Laaksonen andKKontturildquoElectrochemical resolution of 15 oxidation states formonolayerprotected gold nanoparticlesrdquo Journal of the American ChemicalSociety vol 125 no 22 pp 6644ndash6645 2003

[14] K S Park M I Kim M-A Woo and H G Park ldquoA label-free method for detecting biological thiols based on blocking ofHg2+-quenching of fluorescent gold nanoclustersrdquo Biosensors ampBioelectronics vol 45 no 1 pp 65ndash69 2013

[15] N L Rosi andC AMirkin ldquoNanostructures in biodiagnosticsrdquoChemical Reviews vol 105 no 4 pp 1547ndash1562 2005

[16] C-A J Lin T-Y Yang C-H Lee et al ldquoSynthesis charac-terization and bioconjugation of fluorescent gold nanoclusterstoward biological labeling applicationsrdquoACS Nano vol 3 no 2pp 395ndash401 2009

[17] FWangW B Tan Y Zhang X P Fan andMQWang ldquoLumi-nescent nanomaterials for biological labellingrdquoNanotechnologyvol 17 no 1 pp R1ndashR13 2006

[18] G Wang T Huang R W Murray L Menard and R G NuzzoldquoNear-IR luminescence of monolayer-protected metal clustersrdquoJournal of the American Chemical Society vol 127 no 3 pp 812ndash813 2005

[19] X Li F Zhang and D Zhao ldquoHighly efficient lanthanideupconverting nanomaterials progresses and challengesrdquo NanoToday vol 8 no 6 pp 643ndash676 2013

[20] I Dıez and R H A Ras ldquoFluorescent silver nanoclustersrdquoNanoscale vol 3 no 5 pp 1963ndash1970 2011

[21] H Xu and K S Suslick ldquoWater-soluble fluorescent silver nano-clustersrdquo Advanced Materials vol 22 no 10 pp 1078ndash10822010

[22] M A H Muhammed and T Pradeep ldquoLuminescent quan-tum clusters of gold as bio-labelsrdquo in Advanced FluorescenceReporters in Chemistry and Biology II vol 9 of Springer Serieson Fluorescence pp 333ndash353 Springer Berlin Germany 2010

[23] I Dıez and RH A Ras ldquoFew-atom silver clusters as fluorescentreportersrdquo inAdvanced Fluorescence Reporters in Chemistry andBiology II vol 9 of Springer Series on Fluorescence pp 307ndash332Springer Berlin Germany 2010

[24] C-A J Lin C-H Lee J-T Hsieh et al ldquoSynthesis of fluo-rescent metallic nanoclusters toward biomedical applicationrecent progress and present challengesrdquo Journal of Medical andBiological Engineering vol 29 no 6 pp 276ndash283 2009

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[26] J Zheng P R Nicovich and RM Dickson ldquoHighly fluorescentnoble-metal quantum dotsrdquo Annual Review of Physical Chem-istry vol 58 pp 409ndash431 2007

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119909

Au25minus119909

nanoclus-ters the 13 th silver atom mattersrdquo Angewandte ChemiemdashInternational Edition vol 53 no 9 pp 2376ndash2380 2014

[29] G A Ozin and S A Mitchell ldquoLigand-free metal clustersrdquoAngewandte Chemie International Edition vol 22 no 9 pp674ndash694 1983

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[31] T Huang and R W Murray ldquoVisible luminescence of water-soluble monolayer-protected gold clustersrdquo Journal of PhysicalChemistry B vol 105 no 50 pp 12498ndash12502 2001

[32] S Link A Beeby S FitzGerald M A El-Sayed T G Schaaffand R LWhetten ldquoVisible to infrared luminescence from a 28-atom gold clusterrdquoThe Journal of Physical Chemistry B vol 106no 13 pp 3410ndash3415 2002

[33] C-CHuang Z Yang K-H Lee andH-T Chang ldquoSynthesis ofhighly fluorescent gold nanoparticles for sensing mercury(II)rdquoAngewandte Chemie International Edition vol 46 no 36 pp6824ndash6828 2007

[34] J Zheng J T Petty and R M Dickson ldquoHigh quantum yieldblue emission from water-soluble Au

8

nanodotsrdquo Journal of theAmericanChemical Society vol 125 no 26 pp 7780ndash7781 2003

[35] N Schaeffer B Tan C Dickinson et al ldquoFluorescent or notSize-dependent fluorescence switching for polymer-stabilizedgold clusters in the 11-17 nm size rangerdquo Chemical Communi-cations no 34 pp 3986ndash3988 2008

[36] B Santiago Gonzalez M J Rodrıguez C Blanco J RivasM A Lopez-Quintela and J M G Martinho ldquoOne stepsynthesis of the smallest photoluminescent and paramagneticPVP-protected gold atomic clustersrdquo Nano Letters vol 10 no10 pp 4217ndash4221 2010

[37] J Xie Y Zheng and J Y Ying ldquoProtein-directed synthesis ofhighly fluorescent gold nanoclustersrdquo Journal of the AmericanChemical Society vol 131 no 3 pp 888ndash889 2009

[38] Y Kong J Chen F Gao et al ldquoNear-infrared fluorescentribonuclease-A-encapsulated gold nanoclusters preparationcharacterization cancer targeting and imagingrdquoNanoscale vol5 no 3 pp 1009ndash1017 2013


[39] W-Y Chen G-Y Lan and H-T Chang ldquoUse of fluorescentDNA-templated goldsilver nanoclusters for the detection ofsulfide ionsrdquo Analytical Chemistry vol 83 no 24 pp 9450ndash9455 2011

[40] J A Annie Ho H C Chang and W T Su ldquoDOPA-mediatedreduction allows the facile synthesis of fluorescent gold nan-oclusters for use as sensing probes for ferric ionsrdquo AnalyticalChemistry vol 84 no 7 pp 3246ndash3253 2012

[41] L Shang R M Dorlich S Brandholt et al ldquoFacile preparationof water-soluble fluorescent gold nanoclusters for cellular imag-ing applicationsrdquo Nanoscale vol 3 no 5 pp 2009ndash2014 2011

[42] V Venkatesh A Shukla S Sivakumar and S Verma ldquoPurine-stabilized green fluorescent gold nanoclusters for cell nucleiimaging applicationsrdquoACSAppliedMaterials and Interfaces vol6 no 3 pp 2185ndash2191 2014

[43] X Liu C Li J Xu et al ldquoSurfactant-free synthesis andfunctionalization of highly fluorescent gold quantum dotsrdquoJournal of Physical Chemistry C vol 112 no 29 pp 10778ndash107832008

[44] C Zhou C Sun M Yu et al ldquoLuminescent gold nanoparticleswith mixed valence states generated from dissociation of poly-meric Au(I) thiolatesrdquo Journal of Physical Chemistry C vol 114no 17 pp 7727ndash7732 2010

[45] Z Luo X Yuan Y Yu et al ldquoFrom aggregation-induced emis-sion of Au(I)-thiolate complexes to ultrabright Au(0)Au(I)-thiolate core-shell nanoclustersrdquo Journal of the American Chem-ical Society vol 134 no 40 pp 16662ndash16670 2012

[46] Y Guo Z Wang H Shao and X Jiang ldquoStable fluorescent goldnanoparticles for detection of Cu2+ with good sensitivity andselectivityrdquo Analyst vol 137 no 2 pp 301ndash304 2012

[47] F Aldeek M A H Muhammed G Palui N Zhan and HMattoussi ldquoGrowth of highly fluorescent polyethylene glycol-and zwitterion-functionalized gold nanoclustersrdquo ACS Nanovol 7 no 3 pp 2509ndash2521 2013

[48] T U B Rao and T Pradeep ldquoLuminescent Ag7

and Ag8

clustersby interfacial synthesisrdquo Angewandte ChemiemdashInternationalEdition vol 49 no 23 pp 3925ndash3929 2010

[49] J-I Nishigaki S Yamazoe S Kohara et al ldquoA twisted bi-icosahedral Au25 cluster enclosed by bulky arenethiolatesrdquoChemical Communications vol 50 no 7 pp 839ndash841 2014

[50] V R Jupally and A Dass ldquoSynthesis of Au130

(SR)50

andAu130minus119909

Ag119909

(SR)50

nanomolecules through core size conversionof larger metal clustersrdquo Physical Chemistry Chemical Physicsvol 16 no 22 pp 10473ndash10479 2014

[51] X Yuan Z Luo Q Zhang et al ldquoSynthesis of highly fluorescentmetal (Ag Au Pt and Cu) nanoclusters by electrostaticallyinduced reversible phase transferrdquo ACS Nano vol 5 no 11 pp8800ndash8808 2011

[52] X Huang Y Luo Z Li et al ldquoBiolabeling hematopoietic systemcells using near-infrared fluorescent gold nanoclustersrdquo TheJournal of Physical Chemistry C vol 115 no 34 pp 16753ndash167632011

[53] D Joseph and K E Geckeler ldquoSynthesis of highly fluorescentgold nanoclusters using egg white proteinsrdquo Colloids andSurfaces B Biointerfaces vol 115 pp 46ndash50 2014

[54] Y-H Lin andW-L Tseng ldquoUltrasensitive sensing of Hg2+ andCH3

Hg+ based on the fluorescence quenching of lysozymeTypeVI-stabilized gold nanoclustersrdquo Analytical Chemistry vol 82no 22 pp 9194ndash9200 2010

[55] J Zheng and R M Dickson ldquoIndividual water-solubledendrimer-encapsulated silver nanodot fluorescencerdquo Journal

of the American Chemical Society vol 124 no 47 pp 13982ndash13983 2002

[56] C I Richards S Choi J-C Hsiang et al ldquoOligonucleotide-stabilizedAg nanocluster fluorophoresrdquo Journal of the AmericanChemical Society vol 130 no 15 pp 5038ndash5039 2008

[57] B Han and E Wang ldquoDNA-templated fluorescent silver nan-oclustersrdquo Analytical and Bioanalytical Chemistry vol 402 no1 pp 129ndash138 2012

[58] D A Tomalia and J M J Frechet ldquoDiscovery of dendrimersand dendritic polymers a brief historical perspectiverdquo Journalof Polymer Science Part A Polymer Chemistry vol 40 no 16pp 2719ndash2728 2002

[59] D A Tomalia ldquoBirth of a new macromolecular architecturedendrimers as quantized building blocks for nanoscale syn-thetic organic chemistryrdquo Aldrichimica Acta vol 37 no 2 pp39ndash57 2004

[60] B Yuping Z Chang D M Vu J P Temirov R B Dyerand J S Martinez ldquoNanoparticle-free synthesis of fluorescentgold nanoclusters at physiological temperaturerdquo The Journal ofPhysical Chemistry C vol 111 no 33 pp 12194ndash12198 2007

[61] Y-C Jao M-K Chen and S-Y Lin ldquoEnhanced quantumyield of dendrimer-entrapped gold nanodots by a specific ion-pair association and microwave irradiation for bioimagingrdquoChemical Communications vol 46 no 15 pp 2626ndash2628 2010

[62] L Maya G Muralidharan T G Thundat and E A KenikldquoPolymer-mediated assembly of gold nanoclustersrdquo Langmuirvol 16 no 24 pp 9151ndash9154 2000

[63] X Huang B Li L Li et al ldquoFacile preparation of highly bluefluorescent metal nanoclusters in organic mediardquo Journal ofPhysical Chemistry C vol 116 no 1 pp 448ndash455 2012

[64] H Duan and S Nie ldquoEtching colloidal gold nanocrystalswith hyperbranched and multivalent polymers a new route tofluorescent and water-soluble atomic clustersrdquo Journal of theAmerican Chemical Society vol 129 no 9 pp 2412ndash2413 2007

[65] I Hussain S Graham Z X Wang et al ldquoSize-controlledsynthesis of near-monodisperse gold nanoparticles in the 1ndash4 nm range using polymeric stabilizersrdquo Journal of the AmericanChemical Society vol 127 no 47 pp 16398ndash16399 2005

[66] Z Wang B Tan I Hussain et al ldquoDesign of polymericstabilizers for size-controlled synthesis of monodisperse goldnanoparticles in waterrdquo Langmuir vol 23 no 2 pp 885ndash8952007

[67] Y Chen X Zheng X Wang C Wang Y Ding and X JiangldquoNear-infrared emitting gold cluster-poly(acrylic acid) hybridnanogelsrdquo ACS Macro Letters vol 3 no 1 pp 74ndash76 2014

[68] C-L Liu H-T Wu Y-H Hsiao et al ldquoInsulin-directed syn-thesis of fluorescent gold nanoclusters preservation of insulinbioactivity and versatility in cell imagingrdquo Angewandte ChemieInternational Edition vol 50 no 31 pp 7056ndash7060 2011

[69] A R Garcia I Rahn S Johnson et al ldquoHuman insulin fibril-assisted synthesis of fluorescent gold nanoclusters in alkalinemedia under physiological temperaturerdquo Colloids and SurfacesB Biointerfaces vol 105 pp 167ndash172 2013

[70] C Guo and J Irudayaraj ldquoFluorescent Ag clusters via a protein-directed approach as a Hg(II) ion sensorrdquo Analytical Chemistryvol 83 no 8 pp 2883ndash2889 2011

[71] H Wei Z Wang L Yang S Tian C Hou and Y LuldquoLysozyme-stabilized gold fluorescent cluster synthesis andapplication as Hg2+ sensorrdquo Analyst vol 135 no 6 pp 1406ndash1410 2010


[72] J Qiao X Mu L Qi J Deng and L Mao ldquoFolic acid-functionalized fluorescent gold nanoclusters with polymers aslinkers for cancer cell imagingrdquoChemical Communications vol49 no 73 pp 8030ndash8032 2013

[73] E S Kryachko and F Remade ldquoComplexes of DNA basesand Watson-Crick base pairs with small neutral gold clustersrdquoJournal of Physical Chemistry B vol 109 no 48 pp 22746ndash22757 2005

[74] M K Shukla M Dubey E Zakar and J Leszczynski ldquoDFTinvestigation of the interaction of gold nanoclusterswith nucleicacid base guanine and the watson-crick guanine-cytosine basepairrdquo Journal of Physical Chemistry C vol 113 no 10 pp 3960ndash3966 2009

[75] R Zhou M Shi X Chen M Wang and H Chen ldquoAtomicallymonodispersed and fluorescent sub-nanometer gold clusterscreated by biomolecule-assisted etching of nanometer-sizedgold particles and rodsrdquo ChemistrymdashA European Journal vol15 no 19 pp 4944ndash4951 2009

[76] T A C Kennedy J L MacLean and J Liu ldquoBlue emitting goldnanoclusters templated by poly-cytosine DNA at low pH andpoly-adenine DNA at neutral pHrdquo Chemical Communicationsvol 48 no 54 pp 6845ndash6847 2012

[77] G Liu Y Shao K Ma Q Cui F Wu and S Xu ldquoSynthesis ofDNA-templated fluorescent gold nanoclustersrdquo Gold Bulletinvol 45 no 2 pp 69ndash74 2012

[78] H Kawasaki H Yamamoto H Fujimori R Arakawa YIwasaki andM Inada ldquoStability of the DMF-protected Au nan-oclusters photochemical dispersion and thermal propertiesrdquoLangmuir vol 26 no 8 pp 5926ndash5933 2010

[79] S Palmal S Basiruddin A R Maity S C Ray and N R JanaldquoThiol-directed synthesis of highly fluorescent gold clusters andtheir conversion into stable imaging nanoprobesrdquo Chemistryvol 19 no 3 pp 943ndash949 2013

[80] H Chen B Li C Wang et al ldquoCharacterization of a fluores-cence probe based on gold nanoclusters for cell and animalimagingrdquo Nanotechnology vol 24 no 5 Article ID 0557042013

[81] Y Zhang Q Hu M C Paau et al ldquoProbing histidine-stabilizedgold nanoclusters product by high-performance liquid chro-matography and mass spectrometryrdquo Journal of Physical Chem-istry C vol 117 no 36 pp 18697ndash18708 2013

[82] X Mu L Qi P Dong et al ldquoFacile one-pot synthesis of l-proline-stabilized fluorescent gold nanoclusters and its appli-cation as sensing probes for serum ironrdquo Biosensors andBioelectronics vol 49 pp 249ndash255 2013

[83] X Yang M Shi R Zhou X Chen and H Chen ldquoBlending ofHAuCl

4

and histidine in aqueous solution a simple approach tothe Au

10

clusterrdquo Nanoscale vol 3 no 6 pp 2596ndash2601 2011[84] R de la Rica L W Chow C-M Horejs et al ldquoA designer

peptide as a template for growing Au nanoclustersrdquo ChemicalCommunications vol 50 no 73 pp 10648ndash10650 2014

[85] Y Wang Y Cui Y Zhao et al ldquoBifunctional peptides thatprecisely biomineralize Au clusters and specifically stain cellnucleirdquo Chemical Communications vol 48 no 6 pp 871ndash8732012

[86] Y Bao H-C Yeh C Zhong et al ldquoFormation and stabilizationof fluorescent gold nanoclusters using small moleculesrdquo Journalof Physical Chemistry C vol 114 no 38 pp 15879ndash15882 2010

[87] C A Simpson C L Farrow P Tian et al ldquoTiopronin goldnanoparticle precursor forms aurophilic ring tetramerrdquo Inor-ganic Chemistry vol 49 no 23 pp 10858ndash10866 2010

[88] X Yuan Y Yu Q Yao Q Zhang and J Xie ldquoFast synthe-sis of thiolated Au

25

nanoclusters via protection-deprotectionmethodrdquo Journal of Physical Chemistry Letters vol 3 no 17 pp2310ndash2314 2012

[89] Y Bao C Zhong D M Vu J P Temirov R B Dyerand J S Martinez ldquoNanoparticle-free synthesis of fluorescentgold nanoclusters at physiological temperaturerdquo The Journal ofPhysical Chemistry C vol 111 no 33 pp 12194ndash12198 2007

[90] Y Shichibu Y Negishi T Tsukuda and T Teranishi ldquoLarge-scale synthesis of thiolated Au

25

clusters via ligand exchangereactions of phosphine-stabilized Au

11

clustersrdquo Journal of theAmerican Chemical Society vol 127 no 39 pp 13464ndash134652005

[91] M Yu C Zhou J Liu J D Hankins and J Zheng ldquoLumi-nescent gold nanoparticles with pH-dependent membraneadsorptionrdquo Journal of the American Chemical Society vol 133no 29 pp 11014ndash11017 2011

[92] M McPartlin R Mason and L Malatesta ldquoNovel clustercomplexes of gold(0)-gold(I)rdquo Journal of the Chemical SocietyD Chemical Communications no 7 p 334 1969

[93] B K Teo X Shi and H Zhang ldquoPure gold cluster of1991991 layered structure a novel 39-metal-atom cluster[(Ph3

P)14

Au39

C1198976

]C1198972

with an interstitial gold atom in a hexag-onal antiprismatic cagerdquo Journal of the American ChemicalSociety vol 114 no 7 pp 2743ndash2745 1992

[94] C E Briant B R C Theobald J W White L K BellD M P Mingos and A J Welch ldquoSynthesis and X-raystructural characterization of the centred icosahedral goldcluster compound [Au

1198973

(PMe2

Ph)10

Cl2

](PF6

)3

the realizationof a theoretical predictionrdquo Journal of the Chemical SocietyChemical Communications no 5 pp 201ndash202 1981

[95] G Schmid R Pfeil R Boese et al ldquoAu55

[P(C6

H5

)3

]12

Cl6

-agold-clusterofanexceptional sizerdquo Chemische BerichteRecueil vol114 no 11 pp 3634ndash3642 1981

[96] W W Weare S M Reed M G Warner and J E HutchisonldquoImproved synthesis of small (d(CORE)approximateto 15 nm)phosphine-stabilized gold nanoparticiesrdquo Journal of the Ameri-can Chemical Society vol 122 no 51 pp 12890ndash12891 2000

[97] X KWan S F Yuan ZW Lin and QMWang ldquoA chiral goldnanocluster Au

20

protected by tetradentate phosphine ligandsrdquoAngewandte Chemie - International Edition vol 53 no 11 pp2923ndash2926 2014

[98] G H Woehrle L O Brown and J E Hutchison ldquoThiol-functionalized 15-nm gold nanoparticles through ligandexchange reactions scope and mechanism of ligand exchangerdquoJournal of the American Chemical Society vol 127 no 7 pp2172ndash2183 2005

[99] M BrustMWalker D Bethell D J Schiffrin and RWhymanldquoSynthesis of thiol-derivatised gold nanoparticles in a two-phase liquid-liquid systemrdquo Journal of the Chemical SocietyChemical Communications no 7 pp 801ndash802 1994

[100] R Jin H Qian Z Wu et al ldquoSize focusing a methodologyfor synthesizing atomically precise gold nanoclustersrdquo Journalof Physical Chemistry Letters vol 1 no 19 pp 2903ndash2910 2010

[101] Z Wu J Suhan and R Jin ldquoOne-pot synthesis of atomicallymonodisperse thiol-functionalized Au

25

nanoclustersrdquo Journalof Materials Chemistry vol 19 no 5 pp 622ndash626 2009

[102] T G Schaaff G Knight M N Shafigullin R F Borkmanand R L Whetten ldquoIsolation and selected properties of a 104kDa gold glutathione cluster compoundrdquo Journal of PhysicalChemistry B vol 102 no 52 pp 10643ndash10646 1998


[103] Y Negishi Y Takasugi S Sato H Yao K Kimura and TTsukuda ldquoMagic-numbered Au

119899

clusters protected by glu-tathione monolayers (n= 18 21 25 28 32 39) Isolation andspectroscopic characterizationrdquo Journal of the American Chem-ical Society vol 126 no 21 pp 6518ndash6519 2004

[104] Y Negishi K Nobusada and T Tsukuda ldquoGlutathione-protected gold clusters revisited bridging the gap betweengold(I)-thiolate complexes and thiolate-protected goldnanocrystalsrdquo Journal of the American Chemical Society vol127 no 14 pp 5261ndash5270 2005

[105] H Zhang Q Liu T Wang et al ldquoFacile preparation ofglutathione-stabilized gold nanoclusters for selective determi-nation of chromium (III) and chromium (VI) in environmentalwater samplesrdquo Analytica Chimica Acta vol 770 pp 140ndash1462013

[106] A C Templeton S Chen S M Gross and R W MurrayldquoWater-soluble isolable gold clusters protected by tioproninand coenzyme amonolayersrdquo Langmuir vol 15 no 1 pp 66ndash761999

[107] D Lee R L Donkers GWang A S Harper and RWMurrayldquoElectrochemistry and optical absorbance and luminescenceof molecule-like Au38 nanoparticlesrdquo Journal of the AmericanChemical Society vol 126 no 19 pp 6193ndash6199 2004

[108] M C Paau C K Lo X Yang and M M F Choi ldquoSynthe-sis of 14 nm 120572-cyclodextrin-protected gold nanoparticles forluminescence sensing of mercury(II) with picomolar detectionlimitrdquo Journal of Physical ChemistryC vol 114 no 38 pp 15995ndash16003 2010

[109] E S Shibu and T Pradeep ldquoQuantum clusters in cavitiestrapped Au

15

in cyclodextrinsrdquo Chemistry of Materials vol 23no 4 pp 989ndash999 2011

[110] H Zhang X Huang L Li et al ldquoPhotoreductive synthesis ofwater-soluble fluorescent metal nanoclustersrdquo Chemical Com-munications vol 48 no 4 pp 567ndash569 2012

[111] Y Shiraishi D Arakawa andN Toshima ldquopH-dependent colorchange of colloidal dispersions of gold nanoclusters effect ofstabilizerrdquo European Physical Journal E vol 8 no 4 pp 377ndash383 2002

[112] L Shang N Azadfar F Stockmar et al ldquoOne-pot synthesis ofnear-infrared fluorescent gold clusters for cellular fluorescencelifetime imagingrdquo Small vol 7 no 18 pp 2614ndash2620 2011

[113] N K Chaki P Singh C V Dharmadhikari and K P Vijayamo-hanan ldquoSingle-electron charging features of larger dodecane-thiol-protected gold nanoclusters electrochemical and scan-ning tunneling microscopy studiesrdquo Langmuir vol 20 no 23pp 10208ndash10217 2004

[114] H Yao K Miki N Nishida A Sasaki and K Kimura ldquoLargeoptical activity of gold nanocluster enantiomers induced by apair of optically active penicillaminesrdquo Journal of the AmericanChemical Society vol 127 no 44 pp 15536ndash15543 2005

[115] X Yang L Gan L Han D Li J Wang and E Wang ldquoFacilepreparation of chiral penicillamine protected gold nanoclustersand their applications in cell imagingrdquo Chemical Communica-tions vol 49 no 23 pp 2302ndash2304 2013

[116] M A H Muhammed S Ramesh S S Sinha S K Pal andT Pradeep ldquoTwo distinct fluorescent quantum clusters of goldstarting from metallic nanoparticles by pH-dependent ligandetchingrdquo Nano Research vol 1 no 4 pp 333ndash340 2008

[117] H Qian Y Zhu and R Jin ldquoSize-Focusing synthesisoptical and electrochemical properties of monodisperseAu38

(SC2

H4

Ph)24

nanoclustersrdquo ACS Nano vol 3 no 11 pp3795ndash3803 2009

[118] H Qian M Zhu Z Wu and R Jin ldquoQuantum sized goldnanoclusters with atomic precisionrdquo Accounts of ChemicalResearch vol 45 no 9 pp 1470ndash1479 2012

[119] T G Schaaff and R L Whetten ldquoControlled Etching of Au SRcluster Compoundsrdquo Journal of Physical Chemistry B vol 103no 44 pp 9394ndash9396 1999

[120] R A Sperling andW J Parak ldquoSurface modification function-alization and bioconjugation of colloidal Inorganic nanoparti-clesrdquo Philosophical Transactions of the Royal Society A Mathe-matical Physical and Engineering Sciences vol 368 no 1915 pp1333ndash1383 2010

[121] S Jiang K Y Win S Liu C P Teng Y Zheng and M-YHan ldquoSurface-functionalized nanoparticles for biosensing andimaging-guided therapeuticsrdquoNanoscale vol 5 no 8 pp 3127ndash3148 2013

[122] N Erathodiyil and J Y Ying ldquoFunctionalization of inorganicnanoparticles for bioimaging applicationsrdquo Accounts of Chemi-cal Research vol 44 no 10 pp 925ndash935 2011

[123] X Le Guevel B Hotzer G Jung and M Schneider ldquoNIR-emitting fluorescent gold nanoclusters doped in silica nanopar-ticlesrdquo Journal of Materials Chemistry vol 21 no 9 pp 2974ndash2981 2011

[124] C A J Lin R A Sperling J K Li et al ldquoDesign of anamphiphilic polymer for nanoparticle coating and functional-izationrdquo Small vol 4 no 3 pp 334ndash341 2008

[125] S-K Sun L-X Dong Y Cao H-R Sun and X-P YanldquoFabrication of multifunctional Gd

2

O3

Au hybrid nanoprobevia a one-step approach for near-infrared fluorescence andmagnetic resonance multimodal imaging in vivordquo AnalyticalChemistry vol 85 no 17 pp 8436ndash8441 2013

[126] J M Abad S F L Mertens M Pita V M Fernandez andD J Schiffrin ldquoFunctionalization of thioctic acid-capped goldnanoparticles for specific immobilization of histidine-taggedproteinsrdquo Journal of the American Chemical Society vol 127 no15 pp 5689ndash5694 2005

[127] F Wen Y Dong L Feng S Wang S Zhang and X ZhangldquoHorseradish peroxidase functionalized fluorescent gold nan-oclusters for hydrogen peroxide sensingrdquo Analytical Chemistryvol 83 no 4 pp 1193ndash1196 2011

[128] Y Chen Y Wang C Wang et al ldquoPapain-directed synthesisof luminescent gold nanoclusters and the sensitive detection ofCu2+rdquo Journal of Colloid and Interface Science vol 396 pp 63ndash68 2013

[129] C Banerjee J Kuchlyan D Banik et al ldquoInteraction of goldnanoclusters with IR light emitting cyanine dyes a systematicfluorescence quenching studyrdquo Physical Chemistry ChemicalPhysics vol 16 no 32 pp 17272ndash17283 2014

[130] Z Wang J H Lee and Y Lu ldquoHighly sensitive lsquoturn-onrsquofluorescent sensor for Hg2+ in aqueous solution based onstructure-switching DNArdquo Chemical Communications no 45pp 6005ndash6007 2008

[131] Z Gu M Zhao Y Sheng L A Bentolila and Y TangldquoDetection of mercury ion by infrared fluorescent protein andits hydrogel-based paper assayrdquo Analytical Chemistry vol 83no 6 pp 2324ndash2329 2011

[132] M Matsushita M M Meijler P Wirsching R A Lerner andK D Janda ldquoA blue fluorescent antibody-cofactor sensor formercuryrdquo Organic Letters vol 7 no 22 pp 4943ndash4946 2005

[133] B Ruttkay-Nedecky J Kudr L Nejdl DMaskova R Kizek andVAdam ldquoG-quadruplexes as sensing probesrdquoMolecules vol 18no 12 pp 14760ndash14779 2013


[134] J Liu and Y Lu ldquoRational Design of lsquoturn-Onrsquo allostericDNAzyme catalytic beacons for aqueous mercury ions withultrahigh sensitivity and selectivityrdquo Angewandte Chemie vol46 no 40 pp 7587ndash7590 2007

[135] P J J Huang and J Liu ldquoSensing parts-per-trillion Cd2+ Hg2+and Pb2+ collectively and individually using phosphorothioateDNAzymesrdquo Analytical Chemistry vol 86 no 12 pp 5999ndash6005 2014

[136] B-C Ye and B-C Yin ldquoHighly sensitive detection of mer-cury(II) ions by fluorescence polarization enhanced by goldnanoparticlesrdquo Angewandte Chemie International Edition vol47 no 44 pp 8386ndash8389 2008

[137] C-W Tseng H-Y Chang J-Y Chang and C-C HuangldquoDetection of mercury ions based on mercury-induced switch-ing of enzyme-like activity of platinumgold nanoparticlesrdquoNanoscale vol 4 no 21 pp 6823ndash6830 2012

[138] M Suresh S K Mishra S Mishra and A Das ldquoThe detectionof Hg2+ by cyanobacteria in aqueousmediardquoChemical Commu-nications no 18 pp 2496ndash2498 2009

[139] Nuriman B Kuswandi andW Verboom ldquoSelective chemosen-sor for Hg(II) ions based on tris[2-(4-phenyldiazenyl)phe-nylaminoethoxy]cyclotriveratrylene in aqueous samplesrdquo Ana-lytica Chimica Acta vol 655 no 1-2 pp 75ndash79 2009

[140] S Voutsadaki G K Tsikalas E Klontzas G E Froudakis andH E Katerinopoulos ldquoA lsquoturn-onrsquo coumarin-based fluorescentsensor with high selectivity formercury ions in aqueousmediardquoChemical Communications vol 46 no 19 pp 3292ndash3294 2010

[141] J Xie Y Zheng and J Y Ying ldquoHighly selective and ultrasen-sitive detection of Hg2+ based on fluorescence quenching of Aunanoclusters by Hg2+-Au+ interactionsrdquo Chemical Communica-tions vol 46 no 6 pp 961ndash963 2010

[142] TMayr I KlimantO SWolfbeis andTWerner ldquoDual lifetimereferenced optical sensor membrane for the determination ofcopper(II) ionsrdquo Analytica Chimica Acta vol 462 no 1 pp 1ndash10 2002

[143] M E Letelier A M Lepe M Faundez et al ldquoPossiblemechanisms underlying copper-induced damage in biologicalmembranes leading to cellular toxicityrdquo Chemico-BiologicalInteractions vol 151 no 2 pp 71ndash82 2005

[144] L M Gaetke and C K Chow ldquoCopper toxicity oxidative stressand antioxidant nutrientsrdquo Toxicology vol 189 no 1-2 pp 147ndash163 2003

[145] W Chen X Tu and X Guo ldquoFluorescent gold nanoparticles-based fluorescence sensor for Cu2+ ionsrdquo Chemical Communi-cations no 13 pp 1736ndash1738 2009

[146] X Tu W Chen and X Guo ldquoFacile one-pot synthesis of near-infrared luminescent gold nanoparticles for sensing copper(II)rdquo Nanotechnology vol 22 no 9 Article ID 095701 2011

[147] Y Xu X Yang S Zhu and Y Dou ldquoSelectively fluorescentsensing of Cu2+ based on lysine-functionalized gold nanoclus-tersrdquo Colloids and Surfaces A Physicochemical and EngineeringAspects vol 450 pp 115ndash120 2014

[148] D Cao J Fan J Qiu Y Tu and J Yan ldquoMasking methodfor improving selectivity of gold nanoclusters in fluorescencedetermination of mercury and copper ionsrdquo Biosensors ampBioelectronics vol 42 no 1 pp 47ndash50 2013

[149] J-A Annie Ho H-C Chang and W-T Su ldquoDOPA-mediatedreduction allows the facile synthesis of fluorescent gold nan-oclusters for use as sensing probes for ferric ionsrdquo AnalyticalChemistry vol 84 no 7 pp 3246ndash3253 2012

[150] Y-C Shiang C-C Huang and H-T Chang ldquoGold nanodot-based luminescent sensor for the detection of hydrogen perox-ide and glucoserdquo Chemical Communications no 23 pp 3437ndash3439 2009

[151] L Hu S Han S Parveen Y Yuan L Zhang and G XuldquoHighly sensitive fluorescent detection of trypsin based onBSA-stabilized gold nanoclustersrdquo Biosensors amp Bioelectronics vol32 no 1 pp 297ndash299 2012

[152] Q Wen Y Gu L J Tang R Q Yu and J-H Jiang ldquoPeptide-templated gold nanocluster beacon as a sensitive label-freesensor for protein post-translational modification enzymesrdquoAnalytical Chemistry vol 85 no 24 pp 11681ndash11685 2013

[153] X Yang Y Luo Y Zhuo Y Feng and S Zhu ldquoNovel synthesisof gold nanoclusters templated with l-tyrosine for selectiveanalyzing tyrosinaserdquo Analytica Chimica Acta vol 840 pp 87ndash92 2014

[154] B Aswathy and G Sony ldquoCu2+ modulated BSA-Au nanoclus-ters a versatile fluorescence turn-on sensor for dopaminerdquoMicrochemical Journal vol 116 pp 151ndash156 2014

[155] Y Tao Y Lin J Ren and X Qu ldquoA dual fluorometric andcolorimetric sensor for dopamine based on BSA-stabilized Aunanoclustersrdquo Biosensors amp Bioelectronics vol 42 no 1 pp 41ndash46 2013

[156] L Li H Liu Y Shen J Zhang and J J Zhu ldquoElectrogeneratedchemiluminescence of Au nanoclusters for the detection ofdopaminerdquo Analytical Chemistry vol 83 no 3 pp 661ndash6652011

[157] H Liu G Yang E S Abdel-Halim and J-J Zhu ldquoHighly selec-tive and ultrasensitive detection of nitrite based on fluorescentgold nanoclustersrdquo Talanta vol 104 pp 135ndash139 2013

[158] X Chen and G A Baker ldquoCholesterol determination usingprotein-templated fluorescent gold nanocluster probesrdquo Ana-lyst vol 138 no 24 pp 7299ndash7302 2013

[159] B Hemmateenejad F Shakerizadeh-Shirazi and F SamarildquoBSA-modified gold nanoclusters for sensing of folic acidrdquoSensors and Actuators B Chemical vol 199 pp 42ndash46 2014

[160] Z Chen S Qian J Chen J Cai S Wu and Z Cai ldquoProtein-templated gold nanoclusters based sensor for off-ondetection ofciprofloxacin with a high selectivityrdquo Talanta vol 94 pp 240ndash245 2012

[161] G-H Yang J-J Shi S Wang et al ldquoFabrication of a boronnitride-gold nanocluster composite and its versatile applicationfor immunoassaysrdquo Chemical Communications vol 49 no 91pp 10757ndash10759 2013

[162] R C Triulzi M Micic S Giordani M Serry W A Chiouand R M Leblanc ldquoImmunoasssay based on the antibody-conjugated PAMAM-dendrimer-gold quantum dot complexrdquoChemical Communications no 48 pp 5068ndash5070 2006

[163] H Lin L Li C Lei et al ldquoImmune-independent and label-free fluorescent assay for Cystatin C detection based on protein-stabilized Au nanoclustersrdquo Biosensors and Bioelectronics vol41 no 1 pp 256ndash261 2013

[164] K Selvaprakash and Y-C Chen ldquoUsing protein-encapsulatedgold nanoclusters as photoluminescent sensing probes forbiomoleculesrdquo Biosensors amp Bioelectronics vol 61 pp 88ndash942014

[165] C-C Huang C-K Chiang Z-H Lin K-H Lee and H-T Chang ldquoBioconjugated gold nanodots and nanoparticlesfor protein assays based on photoluminescence quenchingrdquoAnalytical Chemistry vol 80 no 5 pp 1497ndash1504 2008


[166] C C Huang C T Chen Y C Shiang Z H Lin and HT Chang ldquoSynthesis of fluorescent carbohydrate-protected Aunanodots for detection of Concanavalin A and Escherichia colirdquoAnalytical Chemistry vol 81 no 3 pp 875ndash882 2009

[167] J Zhang M Sajid N Na L Huang D He and J Ouyang ldquoTheapplication of Au nanoclusters in the fluorescence imaging ofhuman serum proteins after native PAGE enhancing detectionby low-temperature plasma treatmentrdquo Biosensors and Bioelec-tronics vol 35 no 1 pp 313ndash318 2012

[168] A M P Hussain S N Sarangi J A Kesarwani and S N SahuldquoAu-nanocluster emission based glucose sensingrdquo Biosensors ampBioelectronics vol 29 no 1 pp 60ndash65 2011

[169] L Jin L Shang S Guo et al ldquoBiomolecule-stabilized Aunanoclusters as a fluorescence probe for sensitive detection ofglucoserdquo Biosensors amp Bioelectronics vol 26 no 5 pp 1965ndash1969 2011

[170] W J Stark ldquoNanoparticles in biological systemsrdquo AngewandteChemie International Edition vol 50 no 6 pp 1242ndash1258 2011

[171] L Shang and G U Nienhaus ldquoSmall fluorescent nanoparticlesat the nano-bio interfacerdquoMaterials Today vol 16 no 3 pp 58ndash66 2013

[172] H-H Wang C A J Lin C H Lee et al ldquoFluorescent goldnanoclusters as a biocompatible marker for in vitro and in vivotracking of endothelial cellsrdquo ACS Nano vol 5 no 6 pp 4337ndash4344 2011

[173] P-H Chan S-Y Wong S-H Lin and Y-C Chen ldquoLysozyme-encapsulated gold nanocluster-based affinity mass spectrom-etry for pathogenic bacteriardquo Rapid Communications in MassSpectrometry vol 27 no 19 pp 2143ndash2148 2013

[174] D Hu Z Sheng S Fang et al ldquoFolate receptor-targeting goldnanoclusters as fluorescence enzyme mimetic nanoprobes fortumor molecular colocalization diagnosisrdquoTheranostics vol 4no 2 pp 142ndash153 2014

[175] P Botella I Ortega M Quesada et al ldquoMultifunctional hybridmaterials for combined photo and chemotherapy of cancerrdquoDalton Transactions vol 41 no 31 pp 9286ndash9296 2012

[176] P Huang J Lin S Wang et al ldquoPhotosensitizer-conjugatedsilica-coated gold nanoclusters for fluorescence imaging-guided photodynamic therapyrdquo Biomaterials vol 34 no 19 pp4643ndash4654 2013

[177] YWang J Chen and J Irudayaraj ldquoNuclear targeting dynamicsof gold nanoclusters for enhanced therapy of HER2+ breastcancerrdquo ACS Nano vol 5 no 12 pp 9718ndash9725 2011

[178] X Wang X Cai J Hu et al ldquoGlutathione-triggered lsquoOff-Onrsquorelease of anticancer drugs from dendrimer-encapsulated goldnanoparticlesrdquo Journal of the American Chemical Society vol135 no 26 pp 9805ndash9810 2013

[179] C-L Liu M-L Ho Y-C Chen et al ldquoThiol-functionalizedgold nanodots two-photon absorption property and imagingin vitrordquo Journal of Physical Chemistry C vol 113 no 50 pp21082ndash21089 2009

[180] Z Zhou C Zhang Q Qian et al ldquoFolic acid-conjugatedsilica capped gold nanoclusters for targeted fluorescenceX-raycomputed tomography imagingrdquo Journal of Nanobiotechnologyvol 11 article 17 2013

[181] J Wang G Zhang Q Li et al ldquoIn vivo self-bio-imagingof tumors through in situ biosynthesized fluorescent goldnanoclustersrdquo Scientific reports vol 3 2013

[182] G Ramakrishna O Varnavski J Kim D Lee and T Good-son ldquoQuantum-sized gold clusters as efficient two-photonabsorbersrdquo Journal of the American Chemical Society vol 130no 15 pp 5032ndash5033 2008

[183] L Polavarapu M Manna and Q-H Xu ldquoBiocompatible glu-tathione capped gold clusters as one- and two-photon excitationfluorescence contrast agents for live cells imagingrdquo Nanoscalevol 3 no 2 pp 429ndash434 2011

[184] T W J Gadella Jr T M Jovin and R M Clegg ldquoFluorescencelifetime imaging microscopy (FLIM) spatial resolution ofmicrostructures on the nanosecond time scalerdquo BiophysicalChemistry vol 48 no 2 pp 221ndash239 1993

[185] A Zhang Y Tu S Qin et al ldquoGold nanoclusters as contrastagents for fluorescent and X-ray dual-modality imagingrdquo Jour-nal of Colloid and Interface Science vol 372 no 1 pp 239ndash2442012

[186] A Retnakumari S Setua DMenon et al ldquoMolecular-receptor-specific non-toxic near-infrared-emitting Au cluster-proteinnanoconjugates for targeted cancer imagingrdquo Nanotechnologyvol 21 no 5 Article ID 055103 2010

Submit your manuscripts athttpwwwhindawicom

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CorrosionInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Polymer ScienceInternational Journal of



CeramicsJournal of


CompositesJournal of

NanoparticlesJournal of



International Journal of

Biomaterials


NanoscienceJournal of

TextilesHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Journal of

NanotechnologyHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

CrystallographyJournal of


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014


CoatingsJournal of

Advances in

Materials Science and EngineeringHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Smart Materials Research



MetallurgyJournal of


BioMed Research International

MaterialsJournal of


Nano

materials


Journal ofNanomaterials


has an extremely high surface-to-volume ratio which canmake the NCs for further surface modification and control-lable bioconjugation With all the above properties AuNCscan be used in a wide range of applications such as biode-tection [14] biosensing [14] biological labeling [15ndash17] andbioimaging [18]

When fluorophores absorb light with a particular wave-length fluorophoreswill then emit energy in a formof fluores-cence equaling to the energy difference between the excitedstate and the ground state Fluorescent probes are the keyfactor in biological fluorescent measurement In last decadesthere are several different classes of fluorescent labels organicfluorophores such as cyanine dyes and fluorescein the rareearth NPs (quantum dots) [19] upconverting NPs andnovel fluorescent dye-doped core-shell nanobeads But theuse of these labels is limited by the poor photostabilitylarge physical size and toxicity of heavy metals [17] Onthe contrary AuNCs show strong photoluminescence goodphotostability and high emission rates large Stokes shift andsize-dependent tunable fluorescence for which they can bemade as an optimum nanomaterial for biological imaginganalysis and sensing Moreover the surfaces of AuNCspossess a subnanometer dimension color tenability facilesynthesis and low toxicity [20 21] Compared with commonfluorophores these advantages establish them to be a novelultrasmall fluorophores in biomedicine application [22ndash24]

In this review we firstly will discuss the origin of fluores-cence of AuNCs Then we will summarize general synthesisstrategies of AuNCs and describe their distinctive propertieswhich are followed by highlighting their fascinating photolu-minescence properties In the second part we will discuss therecent advances of AuNCs-based application to the biologicallabeling and fluorescent imaging In the final section we willgive a brief outlook on the challenges and prospective forfuture research of AuNCs

2 Gold Nanoclusters FluorescenceProperty and Synthetic Method

21 Fluorescence Mechanism of AuNCs Gold nanomaterialscan be broadly categorized into two kinds according to theirdimensions gold nanoparticles and gold nanoclusters Zhenghas introduced the differences in structures and other prop-erties between these two gold nanomaterials [25] As hemen-tioned gold nanoparticles which sizes are close to the wave-length of light have similar optical properties to bulk goldWhat is more the collective oscillation of conduction elec-trons on the surface of gold nanoparticles can interact withlight and generate SPR effect when the frequency of oscil-lating electrons matches the frequency of incident photonsAnd when the gold nanoparticles have a dimension in 3ndash100 nm the SPR band locates in the visible light region whichwill lead to some size-dependent effects of gold NPs Theinteraction between nanoparticles the dielectric mediumand the protective ligands also has influences on the SPReffect of gold NPs

When size of gold nanomaterials is smaller than 3 nm thegold nanoclusters possess some distinguished properties dueto their ultrasmall dimension and special structure Because

the energy level spacing is inversely proportional to the radiusof AuNCs AuNCs with a dimension close to Fermi wave-length of an electron possess size-dependent electronic struc-ture [26]TheAuNCswe are discussing in this review are sub-nanoscale nanoparticles which have a gold center containinga countable number of gold atoms So AuNCs are consideredas superatoms or molecular-like species For these reasonsthe energy level spacing and free electronic density of AuNCsare the key factors of transition energy of AuNCs When theenergy level spacing is large enough the free electrons behav-ior can be observed in the discrete energy levels [27] Accord-ing to the structural analysis of Jinrsquos group the fluorescence ofAuNCs originates from the LUMO-HOMO transition [28]To sum up the distinct optical properties (absorption andfluorescence) ofmolecular-like AuNCs aremainly affected bytheir ultrasmall size and corresponding electronic structure

In addition to the ultrasmall size the ligands used forAuNCs preparation also have impacts on their fluorescenceproperties [5] Ligands play very important roles in theformation of AuNCs as protective agents which can preventthe superatoms from aggregation and then keep the size-dependent fluorescence property As for the demonstrationthat Jin and coworkers mentioned surface ligands of AuNCsnot only can be used as capping agent but also largelyaffect the fluorescence of AuNCs by charging transfer fromsurface ligand to the gold core When the surface ligandshave strong electron donation capability the fluorescencecan be enhanced And the ligands with electron-rich atomsor groups have been found as a very effective choice forpromising surface ligand of AuNCs to enhance the fluores-cence In this paper we will discuss the synthesis of AuNCsby using different ligands such as glutathione dendrimerspolymers and protein the as-prepared AuNCs based on dif-ferent synthetic methods have various fluorescence quantumyield (QY) Lots of researches have been carried out on theorigin of fluorescence from AuNCs and the enhancementof fluorescence QY for the practical application such asbiological labeling sensing and imaging In this section wehave summarized the different fluorescence QYs of AuNCswith different synthetic routes (Table 1)

22 Synthetic Methods of AuNCs Small gold nanoclusterswith robust quantum effect have been extensively investi-gated The synthesis of AuNCs experiences several stages Inthe early time the research was focused on gas state metalclusters [29] Since these metal clusters in the gas phase wereshort-lived and hard to be functionalized a novel methodsolution-phase synthesis arose in the 1980s [30 31] Thesesynthetic strategies lead to gold nanoclusters with enhancedstability and excellent physicochemical properties

Since Brust et al reported the synthesis of monolayerprotected metal nanoparticles several novel advances haveemerged in the field of metal nanoclusters especially in thefield of thiol-containing AuNCs During the decades thesynthetic strategies were generally considered as two routesldquoAtoms to Clustersrdquo and ldquoNanoparticles to Clustersrdquo Theapproach of ldquoAtoms to Clustersrdquo is to reduce the gold ionsinto zerovalent atoms and then AuNCs are formed with thenucleation of the Au atoms However the gold precursors












8



4

G4NH2

pairand AuBr

4



15000

10000

5000

0

400300 500 600 700

Wavelength (nm)

Inte

nsity

(a)

(b)




4


2


4


Tumor

Cysteamine

NIR


HAuCl4 NaBH4


BSA AuCl4

BSA-Au NC

Incubate 12h

+ NaOH

Incubate 2min

+

BSA-Au ion complex









UV light



(a) (b)

NO

H

N

O

H N

O

H

NOH



4




(PPh3

)7

(SCN)3



55


20


2

) Cl [PPhpy2


4

the Au20



Glutathione (GSH)

in water


sim70mgAu25(SG)18

328K15h



two Au11


25

(SG)18



38


38




4



119899

(SR)119898


2

H4

Ph -SC12

H25

SG and SC10

H22

COOH)[101]



4


119899

(SR)119898





(a)

300 400 500 600 700 800

Wavelength (nm)

Abso

rban

ce

Fluo

resc

ence


(b)



38

(SC2

H4

Ph)24





4



(a)

10

08

06

04

02

00

200 300 400 500 600 700 800

Wavelength (nm)

A(a

u)

(b)

(c) (d)









Aqueous

AuSR

Ethanol Ethanol

H2O H2O

Denseaggregates



Oligomericcomplexes

Nonemissive

75 ethanol

95 ethanolh

h

[ ]n

(a)

fe 0 30 60 65 70 75 80 85 90 95()

(b)

Abso

rban

ce (a

u)


95

90

85

80

75

70

65

60

30

0

(c)

PL in

tens

ity (a

u)

PL in

ten

(au

)

0 20 40 60 80 100fe (vol)

70

65

60

30

0

95

90

85

80

75


(d)


119890


119890


119890













3


3



Li+

Na+ K+

Mg2

+

Ca2+

Ba2+

Fe2+

Fe2+

Co2

+

Ni2+

Cu2+

Zn2+

Mn2

+

Ag+

Cd2

+

Pb2+

Cr3+

CH3H

g+

Hg2

+

CH3H

g++

Hg2

+

0

01

02

Sr2+

(IF0minusI F

)I F

0

(a)

0

01

02

F∙ Cl∙

Br∙

Citr

ate3

∙Ac

O∙I∙

(IF0minusI F

)I F

0

ClO4∙

BrO

3∙

IO3∙

NO

2∙

NO

3∙

CO32∙

HCO

3∙

SO32∙

SO42∙

S 2O32∙

PO42∙

HPO

42∙

H2P

O4∙

BO33∙

(b)


minus 119868119865

)1198681198650


3


1198650

and 119868119865





h998400 h998400

h h

H2O2

HRP-AuNCsHRP

(a)

0

100nM250nM500nM1120583M5120583M10120583M25120583M50120583M100120583M

400 450 500 550 600 650 700

0

50

100

150

200

250

300

350

FL in

tens

ity (a

u) 35

40

45

50

55

01 05 1 5 10

I 450l 4

50

120582 (nm)

[H2O2] (120583M)

(b)


O2






O2








Apt-Q AuNP

Apt-QAuNPPDGFs

Apt-QAuNP

PDGF receptor

FRET

FRET

FRET

h 998400h

h 998400h

h 998400h

PDGF receptor

(a)

(b)

(c)

AuNDPDGF AA-L

AuNPApt-Q



2

O2


2

O2





ApoptosisCyt C

Cellular uptake

Endosome


Mitochondria



2






25




50120583m

(a)

50120583m

(b)

50120583m

(c)

50120583m

(d)






2


2



2

O3


119881

1205733

integrin in U87


(a)

(b)

(d)

(e)

(c)

DN

A d

amag

e rat

e

0

20

40

60

80

100


(f)



O3


O3

Au (RGD-Gd2

O3





5000

19500

33000

46500

60000

(a)

25000

37500

50000

62500

75000

(b)

45250

59922

74588

89254

(c)

Figure 15 AuNCsSiO2



2










Fluorescent imaging

Incubation for

24h or 48h


HAuCl4

h

Gold-nanocluster

Tumor

(a)

Scal

ed (c

ount

ss)

0

001(b) (c) (d)


4



4






Acknowledgments


References






























119909

Au25minus119909








8

















and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials














8



4

G4NH2

pairand AuBr

4



15000

10000

5000

0

400300 500 600 700

Wavelength (nm)

Inte

nsity

(a)

(b)




4


2


4


Tumor

Cysteamine

NIR


HAuCl4 NaBH4


BSA AuCl4

BSA-Au NC

Incubate 12h

+ NaOH

Incubate 2min

+

BSA-Au ion complex









UV light



(a) (b)

NO

H

N

O

H N

O

H

NOH



4




(PPh3

)7

(SCN)3



55


20


2

) Cl [PPhpy2


4

the Au20



Glutathione (GSH)

in water


sim70mgAu25(SG)18

328K15h



two Au11


25

(SG)18



38


38




4



119899

(SR)119898


2

H4

Ph -SC12

H25

SG and SC10

H22

COOH)[101]



4


119899

(SR)119898





(a)

300 400 500 600 700 800

Wavelength (nm)

Abso

rban

ce

Fluo

resc

ence


(b)



38

(SC2

H4

Ph)24





4



(a)

10

08

06

04

02

00

200 300 400 500 600 700 800

Wavelength (nm)

A(a

u)

(b)

(c) (d)









Aqueous

AuSR

Ethanol Ethanol

H2O H2O

Denseaggregates



Oligomericcomplexes

Nonemissive

75 ethanol

95 ethanolh

h

[ ]n

(a)

fe 0 30 60 65 70 75 80 85 90 95()

(b)

Abso

rban

ce (a

u)


95

90

85

80

75

70

65

60

30

0

(c)

PL in

tens

ity (a

u)

PL in

ten

(au

)

0 20 40 60 80 100fe (vol)

70

65

60

30

0

95

90

85

80

75


(d)


119890


119890


119890













3


3



Li+

Na+ K+

Mg2

+

Ca2+

Ba2+

Fe2+

Fe2+

Co2

+

Ni2+

Cu2+

Zn2+

Mn2

+

Ag+

Cd2

+

Pb2+

Cr3+

CH3H

g+

Hg2

+

CH3H

g++

Hg2

+

0

01

02

Sr2+

(IF0minusI F

)I F

0

(a)

0

01

02

F∙ Cl∙

Br∙

Citr

ate3

∙Ac

O∙I∙

(IF0minusI F

)I F

0

ClO4∙

BrO

3∙

IO3∙

NO

2∙

NO

3∙

CO32∙

HCO

3∙

SO32∙

SO42∙

S 2O32∙

PO42∙

HPO

42∙

H2P

O4∙

BO33∙

(b)


minus 119868119865

)1198681198650


3


1198650

and 119868119865





h998400 h998400

h h

H2O2

HRP-AuNCsHRP

(a)

0

100nM250nM500nM1120583M5120583M10120583M25120583M50120583M100120583M

400 450 500 550 600 650 700

0

50

100

150

200

250

300

350

FL in

tens

ity (a

u) 35

40

45

50

55

01 05 1 5 10

I 450l 4

50

120582 (nm)

[H2O2] (120583M)

(b)


O2






O2








Apt-Q AuNP

Apt-QAuNPPDGFs

Apt-QAuNP

PDGF receptor

FRET

FRET

FRET

h 998400h

h 998400h

h 998400h

PDGF receptor

(a)

(b)

(c)

AuNDPDGF AA-L

AuNPApt-Q



2

O2


2

O2





ApoptosisCyt C

Cellular uptake

Endosome


Mitochondria



2






25




50120583m

(a)

50120583m

(b)

50120583m

(c)

50120583m

(d)






2


2



2

O3


119881

1205733

integrin in U87


(a)

(b)

(d)

(e)

(c)

DN

A d

amag

e rat

e

0

20

40

60

80

100


(f)



O3


O3

Au (RGD-Gd2

O3





5000

19500

33000

46500

60000

(a)

25000

37500

50000

62500

75000

(b)

45250

59922

74588

89254

(c)

Figure 15 AuNCsSiO2



2










Fluorescent imaging

Incubation for

24h or 48h


HAuCl4

h

Gold-nanocluster

Tumor

(a)

Scal

ed (c

ount

ss)

0

001(b) (c) (d)


4



4






Acknowledgments


References






























119909

Au25minus119909








8

















and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials




15000

10000

5000

0

400300 500 600 700

Wavelength (nm)

Inte

nsity

(a)

(b)




4


2


4


Tumor

Cysteamine

NIR


HAuCl4 NaBH4


BSA AuCl4

BSA-Au NC

Incubate 12h

+ NaOH

Incubate 2min

+

BSA-Au ion complex









UV light



(a) (b)

NO

H

N

O

H N

O

H

NOH



4




(PPh3

)7

(SCN)3



55


20


2

) Cl [PPhpy2


4

the Au20



Glutathione (GSH)

in water


sim70mgAu25(SG)18

328K15h



two Au11


25

(SG)18



38


38




4



119899

(SR)119898


2

H4

Ph -SC12

H25

SG and SC10

H22

COOH)[101]



4


119899

(SR)119898





(a)

300 400 500 600 700 800

Wavelength (nm)

Abso

rban

ce

Fluo

resc

ence


(b)



38

(SC2

H4

Ph)24





4



(a)

10

08

06

04

02

00

200 300 400 500 600 700 800

Wavelength (nm)

A(a

u)

(b)

(c) (d)









Aqueous

AuSR

Ethanol Ethanol

H2O H2O

Denseaggregates



Oligomericcomplexes

Nonemissive

75 ethanol

95 ethanolh

h

[ ]n

(a)

fe 0 30 60 65 70 75 80 85 90 95()

(b)

Abso

rban

ce (a

u)


95

90

85

80

75

70

65

60

30

0

(c)

PL in

tens

ity (a

u)

PL in

ten

(au

)

0 20 40 60 80 100fe (vol)

70

65

60

30

0

95

90

85

80

75


(d)


119890


119890


119890













3


3



Li+

Na+ K+

Mg2

+

Ca2+

Ba2+

Fe2+

Fe2+

Co2

+

Ni2+

Cu2+

Zn2+

Mn2

+

Ag+

Cd2

+

Pb2+

Cr3+

CH3H

g+

Hg2

+

CH3H

g++

Hg2

+

0

01

02

Sr2+

(IF0minusI F

)I F

0

(a)

0

01

02

F∙ Cl∙

Br∙

Citr

ate3

∙Ac

O∙I∙

(IF0minusI F

)I F

0

ClO4∙

BrO

3∙

IO3∙

NO

2∙

NO

3∙

CO32∙

HCO

3∙

SO32∙

SO42∙

S 2O32∙

PO42∙

HPO

42∙

H2P

O4∙

BO33∙

(b)


minus 119868119865

)1198681198650


3


1198650

and 119868119865





h998400 h998400

h h

H2O2

HRP-AuNCsHRP

(a)

0

100nM250nM500nM1120583M5120583M10120583M25120583M50120583M100120583M

400 450 500 550 600 650 700

0

50

100

150

200

250

300

350

FL in

tens

ity (a

u) 35

40

45

50

55

01 05 1 5 10

I 450l 4

50

120582 (nm)

[H2O2] (120583M)

(b)


O2






O2








Apt-Q AuNP

Apt-QAuNPPDGFs

Apt-QAuNP

PDGF receptor

FRET

FRET

FRET

h 998400h

h 998400h

h 998400h

PDGF receptor

(a)

(b)

(c)

AuNDPDGF AA-L

AuNPApt-Q



2

O2


2

O2





ApoptosisCyt C

Cellular uptake

Endosome


Mitochondria



2






25




50120583m

(a)

50120583m

(b)

50120583m

(c)

50120583m

(d)






2


2



2

O3


119881

1205733

integrin in U87


(a)

(b)

(d)

(e)

(c)

DN

A d

amag

e rat

e

0

20

40

60

80

100


(f)



O3


O3

Au (RGD-Gd2

O3





5000

19500

33000

46500

60000

(a)

25000

37500

50000

62500

75000

(b)

45250

59922

74588

89254

(c)

Figure 15 AuNCsSiO2



2










Fluorescent imaging

Incubation for

24h or 48h


HAuCl4

h

Gold-nanocluster

Tumor

(a)

Scal

ed (c

ount

ss)

0

001(b) (c) (d)


4



4






Acknowledgments


References






























119909

Au25minus119909








8

















and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials







UV light



(a) (b)

NO

H

N

O

H N

O

H

NOH



4




(PPh3

)7

(SCN)3



55


20


2

) Cl [PPhpy2


4

the Au20



Glutathione (GSH)

in water


sim70mgAu25(SG)18

328K15h



two Au11


25

(SG)18



38


38




4



119899

(SR)119898


2

H4

Ph -SC12

H25

SG and SC10

H22

COOH)[101]



4


119899

(SR)119898





(a)

300 400 500 600 700 800

Wavelength (nm)

Abso

rban

ce

Fluo

resc

ence


(b)



38

(SC2

H4

Ph)24





4



(a)

10

08

06

04

02

00

200 300 400 500 600 700 800

Wavelength (nm)

A(a

u)

(b)

(c) (d)









Aqueous

AuSR

Ethanol Ethanol

H2O H2O

Denseaggregates



Oligomericcomplexes

Nonemissive

75 ethanol

95 ethanolh

h

[ ]n

(a)

fe 0 30 60 65 70 75 80 85 90 95()

(b)

Abso

rban

ce (a

u)


95

90

85

80

75

70

65

60

30

0

(c)

PL in

tens

ity (a

u)

PL in

ten

(au

)

0 20 40 60 80 100fe (vol)

70

65

60

30

0

95

90

85

80

75


(d)


119890


119890


119890













3


3



Li+

Na+ K+

Mg2

+

Ca2+

Ba2+

Fe2+

Fe2+

Co2

+

Ni2+

Cu2+

Zn2+

Mn2

+

Ag+

Cd2

+

Pb2+

Cr3+

CH3H

g+

Hg2

+

CH3H

g++

Hg2

+

0

01

02

Sr2+

(IF0minusI F

)I F

0

(a)

0

01

02

F∙ Cl∙

Br∙

Citr

ate3

∙Ac

O∙I∙

(IF0minusI F

)I F

0

ClO4∙

BrO

3∙

IO3∙

NO

2∙

NO

3∙

CO32∙

HCO

3∙

SO32∙

SO42∙

S 2O32∙

PO42∙

HPO

42∙

H2P

O4∙

BO33∙

(b)


minus 119868119865

)1198681198650


3


1198650

and 119868119865





h998400 h998400

h h

H2O2

HRP-AuNCsHRP

(a)

0

100nM250nM500nM1120583M5120583M10120583M25120583M50120583M100120583M

400 450 500 550 600 650 700

0

50

100

150

200

250

300

350

FL in

tens

ity (a

u) 35

40

45

50

55

01 05 1 5 10

I 450l 4

50

120582 (nm)

[H2O2] (120583M)

(b)


O2






O2








Apt-Q AuNP

Apt-QAuNPPDGFs

Apt-QAuNP

PDGF receptor

FRET

FRET

FRET

h 998400h

h 998400h

h 998400h

PDGF receptor

(a)

(b)

(c)

AuNDPDGF AA-L

AuNPApt-Q



2

O2


2

O2





ApoptosisCyt C

Cellular uptake

Endosome


Mitochondria



2






25




50120583m

(a)

50120583m

(b)

50120583m

(c)

50120583m

(d)






2


2



2

O3


119881

1205733

integrin in U87


(a)

(b)

(d)

(e)

(c)

DN

A d

amag

e rat

e

0

20

40

60

80

100


(f)



O3


O3

Au (RGD-Gd2

O3





5000

19500

33000

46500

60000

(a)

25000

37500

50000

62500

75000

(b)

45250

59922

74588

89254

(c)

Figure 15 AuNCsSiO2



2










Fluorescent imaging

Incubation for

24h or 48h


HAuCl4

h

Gold-nanocluster

Tumor

(a)

Scal

ed (c

ount

ss)

0

001(b) (c) (d)


4



4






Acknowledgments


References






























119909

Au25minus119909








8

















and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials




Glutathione (GSH)

in water


sim70mgAu25(SG)18

328K15h



two Au11


25

(SG)18



38


38




4



119899

(SR)119898


2

H4

Ph -SC12

H25

SG and SC10

H22

COOH)[101]



4


119899

(SR)119898





(a)

300 400 500 600 700 800

Wavelength (nm)

Abso

rban

ce

Fluo

resc

ence


(b)



38

(SC2

H4

Ph)24





4



(a)

10

08

06

04

02

00

200 300 400 500 600 700 800

Wavelength (nm)

A(a

u)

(b)

(c) (d)









Aqueous

AuSR

Ethanol Ethanol

H2O H2O

Denseaggregates



Oligomericcomplexes

Nonemissive

75 ethanol

95 ethanolh

h

[ ]n

(a)

fe 0 30 60 65 70 75 80 85 90 95()

(b)

Abso

rban

ce (a

u)


95

90

85

80

75

70

65

60

30

0

(c)

PL in

tens

ity (a

u)

PL in

ten

(au

)

0 20 40 60 80 100fe (vol)

70

65

60

30

0

95

90

85

80

75


(d)


119890


119890


119890













3


3



Li+

Na+ K+

Mg2

+

Ca2+

Ba2+

Fe2+

Fe2+

Co2

+

Ni2+

Cu2+

Zn2+

Mn2

+

Ag+

Cd2

+

Pb2+

Cr3+

CH3H

g+

Hg2

+

CH3H

g++

Hg2

+

0

01

02

Sr2+

(IF0minusI F

)I F

0

(a)

0

01

02

F∙ Cl∙

Br∙

Citr

ate3

∙Ac

O∙I∙

(IF0minusI F

)I F

0

ClO4∙

BrO

3∙

IO3∙

NO

2∙

NO

3∙

CO32∙

HCO

3∙

SO32∙

SO42∙

S 2O32∙

PO42∙

HPO

42∙

H2P

O4∙

BO33∙

(b)


minus 119868119865

)1198681198650


3


1198650

and 119868119865





h998400 h998400

h h

H2O2

HRP-AuNCsHRP

(a)

0

100nM250nM500nM1120583M5120583M10120583M25120583M50120583M100120583M

400 450 500 550 600 650 700

0

50

100

150

200

250

300

350

FL in

tens

ity (a

u) 35

40

45

50

55

01 05 1 5 10

I 450l 4

50

120582 (nm)

[H2O2] (120583M)

(b)


O2






O2








Apt-Q AuNP

Apt-QAuNPPDGFs

Apt-QAuNP

PDGF receptor

FRET

FRET

FRET

h 998400h

h 998400h

h 998400h

PDGF receptor

(a)

(b)

(c)

AuNDPDGF AA-L

AuNPApt-Q



2

O2


2

O2





ApoptosisCyt C

Cellular uptake

Endosome


Mitochondria



2






25




50120583m

(a)

50120583m

(b)

50120583m

(c)

50120583m

(d)






2


2



2

O3


119881

1205733

integrin in U87


(a)

(b)

(d)

(e)

(c)

DN

A d

amag

e rat

e

0

20

40

60

80

100


(f)



O3


O3

Au (RGD-Gd2

O3





5000

19500

33000

46500

60000

(a)

25000

37500

50000

62500

75000

(b)

45250

59922

74588

89254

(c)

Figure 15 AuNCsSiO2



2










Fluorescent imaging

Incubation for

24h or 48h


HAuCl4

h

Gold-nanocluster

Tumor

(a)

Scal

ed (c

ount

ss)

0

001(b) (c) (d)


4



4






Acknowledgments


References






























119909

Au25minus119909








8

















and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials




(a)

300 400 500 600 700 800

Wavelength (nm)

Abso

rban

ce

Fluo

resc

ence


(b)



38

(SC2

H4

Ph)24





4



(a)

10

08

06

04

02

00

200 300 400 500 600 700 800

Wavelength (nm)

A(a

u)

(b)

(c) (d)









Aqueous

AuSR

Ethanol Ethanol

H2O H2O

Denseaggregates



Oligomericcomplexes

Nonemissive

75 ethanol

95 ethanolh

h

[ ]n

(a)

fe 0 30 60 65 70 75 80 85 90 95()

(b)

Abso

rban

ce (a

u)


95

90

85

80

75

70

65

60

30

0

(c)

PL in

tens

ity (a

u)

PL in

ten

(au

)

0 20 40 60 80 100fe (vol)

70

65

60

30

0

95

90

85

80

75


(d)


119890


119890


119890













3


3



Li+

Na+ K+

Mg2

+

Ca2+

Ba2+

Fe2+

Fe2+

Co2

+

Ni2+

Cu2+

Zn2+

Mn2

+

Ag+

Cd2

+

Pb2+

Cr3+

CH3H

g+

Hg2

+

CH3H

g++

Hg2

+

0

01

02

Sr2+

(IF0minusI F

)I F

0

(a)

0

01

02

F∙ Cl∙

Br∙

Citr

ate3

∙Ac

O∙I∙

(IF0minusI F

)I F

0

ClO4∙

BrO

3∙

IO3∙

NO

2∙

NO

3∙

CO32∙

HCO

3∙

SO32∙

SO42∙

S 2O32∙

PO42∙

HPO

42∙

H2P

O4∙

BO33∙

(b)


minus 119868119865

)1198681198650


3


1198650

and 119868119865





h998400 h998400

h h

H2O2

HRP-AuNCsHRP

(a)

0

100nM250nM500nM1120583M5120583M10120583M25120583M50120583M100120583M

400 450 500 550 600 650 700

0

50

100

150

200

250

300

350

FL in

tens

ity (a

u) 35

40

45

50

55

01 05 1 5 10

I 450l 4

50

120582 (nm)

[H2O2] (120583M)

(b)


O2






O2








Apt-Q AuNP

Apt-QAuNPPDGFs

Apt-QAuNP

PDGF receptor

FRET

FRET

FRET

h 998400h

h 998400h

h 998400h

PDGF receptor

(a)

(b)

(c)

AuNDPDGF AA-L

AuNPApt-Q



2

O2


2

O2





ApoptosisCyt C

Cellular uptake

Endosome


Mitochondria



2






25




50120583m

(a)

50120583m

(b)

50120583m

(c)

50120583m

(d)






2


2



2

O3


119881

1205733

integrin in U87


(a)

(b)

(d)

(e)

(c)

DN

A d

amag

e rat

e

0

20

40

60

80

100


(f)



O3


O3

Au (RGD-Gd2

O3





5000

19500

33000

46500

60000

(a)

25000

37500

50000

62500

75000

(b)

45250

59922

74588

89254

(c)

Figure 15 AuNCsSiO2



2










Fluorescent imaging

Incubation for

24h or 48h


HAuCl4

h

Gold-nanocluster

Tumor

(a)

Scal

ed (c

ount

ss)

0

001(b) (c) (d)


4



4






Acknowledgments


References






























119909

Au25minus119909








8

















and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials




(a)

10

08

06

04

02

00

200 300 400 500 600 700 800

Wavelength (nm)

A(a

u)

(b)

(c) (d)









Aqueous

AuSR

Ethanol Ethanol

H2O H2O

Denseaggregates



Oligomericcomplexes

Nonemissive

75 ethanol

95 ethanolh

h

[ ]n

(a)

fe 0 30 60 65 70 75 80 85 90 95()

(b)

Abso

rban

ce (a

u)


95

90

85

80

75

70

65

60

30

0

(c)

PL in

tens

ity (a

u)

PL in

ten

(au

)

0 20 40 60 80 100fe (vol)

70

65

60

30

0

95

90

85

80

75


(d)


119890


119890


119890













3


3



Li+

Na+ K+

Mg2

+

Ca2+

Ba2+

Fe2+

Fe2+

Co2

+

Ni2+

Cu2+

Zn2+

Mn2

+

Ag+

Cd2

+

Pb2+

Cr3+

CH3H

g+

Hg2

+

CH3H

g++

Hg2

+

0

01

02

Sr2+

(IF0minusI F

)I F

0

(a)

0

01

02

F∙ Cl∙

Br∙

Citr

ate3

∙Ac

O∙I∙

(IF0minusI F

)I F

0

ClO4∙

BrO

3∙

IO3∙

NO

2∙

NO

3∙

CO32∙

HCO

3∙

SO32∙

SO42∙

S 2O32∙

PO42∙

HPO

42∙

H2P

O4∙

BO33∙

(b)


minus 119868119865

)1198681198650


3


1198650

and 119868119865





h998400 h998400

h h

H2O2

HRP-AuNCsHRP

(a)

0

100nM250nM500nM1120583M5120583M10120583M25120583M50120583M100120583M

400 450 500 550 600 650 700

0

50

100

150

200

250

300

350

FL in

tens

ity (a

u) 35

40

45

50

55

01 05 1 5 10

I 450l 4

50

120582 (nm)

[H2O2] (120583M)

(b)


O2






O2








Apt-Q AuNP

Apt-QAuNPPDGFs

Apt-QAuNP

PDGF receptor

FRET

FRET

FRET

h 998400h

h 998400h

h 998400h

PDGF receptor

(a)

(b)

(c)

AuNDPDGF AA-L

AuNPApt-Q



2

O2


2

O2





ApoptosisCyt C

Cellular uptake

Endosome


Mitochondria



2






25




50120583m

(a)

50120583m

(b)

50120583m

(c)

50120583m

(d)






2


2



2

O3


119881

1205733

integrin in U87


(a)

(b)

(d)

(e)

(c)

DN

A d

amag

e rat

e

0

20

40

60

80

100


(f)



O3


O3

Au (RGD-Gd2

O3





5000

19500

33000

46500

60000

(a)

25000

37500

50000

62500

75000

(b)

45250

59922

74588

89254

(c)

Figure 15 AuNCsSiO2



2










Fluorescent imaging

Incubation for

24h or 48h


HAuCl4

h

Gold-nanocluster

Tumor

(a)

Scal

ed (c

ount

ss)

0

001(b) (c) (d)


4



4






Acknowledgments


References






























119909

Au25minus119909








8

















and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials




Aqueous

AuSR

Ethanol Ethanol

H2O H2O

Denseaggregates



Oligomericcomplexes

Nonemissive

75 ethanol

95 ethanolh

h

[ ]n

(a)

fe 0 30 60 65 70 75 80 85 90 95()

(b)

Abso

rban

ce (a

u)


95

90

85

80

75

70

65

60

30

0

(c)

PL in

tens

ity (a

u)

PL in

ten

(au

)

0 20 40 60 80 100fe (vol)

70

65

60

30

0

95

90

85

80

75


(d)


119890


119890


119890













3


3



Li+

Na+ K+

Mg2

+

Ca2+

Ba2+

Fe2+

Fe2+

Co2

+

Ni2+

Cu2+

Zn2+

Mn2

+

Ag+

Cd2

+

Pb2+

Cr3+

CH3H

g+

Hg2

+

CH3H

g++

Hg2

+

0

01

02

Sr2+

(IF0minusI F

)I F

0

(a)

0

01

02

F∙ Cl∙

Br∙

Citr

ate3

∙Ac

O∙I∙

(IF0minusI F

)I F

0

ClO4∙

BrO

3∙

IO3∙

NO

2∙

NO

3∙

CO32∙

HCO

3∙

SO32∙

SO42∙

S 2O32∙

PO42∙

HPO

42∙

H2P

O4∙

BO33∙

(b)


minus 119868119865

)1198681198650


3


1198650

and 119868119865





h998400 h998400

h h

H2O2

HRP-AuNCsHRP

(a)

0

100nM250nM500nM1120583M5120583M10120583M25120583M50120583M100120583M

400 450 500 550 600 650 700

0

50

100

150

200

250

300

350

FL in

tens

ity (a

u) 35

40

45

50

55

01 05 1 5 10

I 450l 4

50

120582 (nm)

[H2O2] (120583M)

(b)


O2






O2








Apt-Q AuNP

Apt-QAuNPPDGFs

Apt-QAuNP

PDGF receptor

FRET

FRET

FRET

h 998400h

h 998400h

h 998400h

PDGF receptor

(a)

(b)

(c)

AuNDPDGF AA-L

AuNPApt-Q



2

O2


2

O2





ApoptosisCyt C

Cellular uptake

Endosome


Mitochondria



2






25




50120583m

(a)

50120583m

(b)

50120583m

(c)

50120583m

(d)






2


2



2

O3


119881

1205733

integrin in U87


(a)

(b)

(d)

(e)

(c)

DN

A d

amag

e rat

e

0

20

40

60

80

100


(f)



O3


O3

Au (RGD-Gd2

O3





5000

19500

33000

46500

60000

(a)

25000

37500

50000

62500

75000

(b)

45250

59922

74588

89254

(c)

Figure 15 AuNCsSiO2



2










Fluorescent imaging

Incubation for

24h or 48h


HAuCl4

h

Gold-nanocluster

Tumor

(a)

Scal

ed (c

ount

ss)

0

001(b) (c) (d)


4



4






Acknowledgments


References






























119909

Au25minus119909








8

















and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials










3


3



Li+

Na+ K+

Mg2

+

Ca2+

Ba2+

Fe2+

Fe2+

Co2

+

Ni2+

Cu2+

Zn2+

Mn2

+

Ag+

Cd2

+

Pb2+

Cr3+

CH3H

g+

Hg2

+

CH3H

g++

Hg2

+

0

01

02

Sr2+

(IF0minusI F

)I F

0

(a)

0

01

02

F∙ Cl∙

Br∙

Citr

ate3

∙Ac

O∙I∙

(IF0minusI F

)I F

0

ClO4∙

BrO

3∙

IO3∙

NO

2∙

NO

3∙

CO32∙

HCO

3∙

SO32∙

SO42∙

S 2O32∙

PO42∙

HPO

42∙

H2P

O4∙

BO33∙

(b)


minus 119868119865

)1198681198650


3


1198650

and 119868119865





h998400 h998400

h h

H2O2

HRP-AuNCsHRP

(a)

0

100nM250nM500nM1120583M5120583M10120583M25120583M50120583M100120583M

400 450 500 550 600 650 700

0

50

100

150

200

250

300

350

FL in

tens

ity (a

u) 35

40

45

50

55

01 05 1 5 10

I 450l 4

50

120582 (nm)

[H2O2] (120583M)

(b)


O2






O2








Apt-Q AuNP

Apt-QAuNPPDGFs

Apt-QAuNP

PDGF receptor

FRET

FRET

FRET

h 998400h

h 998400h

h 998400h

PDGF receptor

(a)

(b)

(c)

AuNDPDGF AA-L

AuNPApt-Q



2

O2


2

O2





ApoptosisCyt C

Cellular uptake

Endosome


Mitochondria



2






25




50120583m

(a)

50120583m

(b)

50120583m

(c)

50120583m

(d)






2


2



2

O3


119881

1205733

integrin in U87


(a)

(b)

(d)

(e)

(c)

DN

A d

amag

e rat

e

0

20

40

60

80

100


(f)



O3


O3

Au (RGD-Gd2

O3





5000

19500

33000

46500

60000

(a)

25000

37500

50000

62500

75000

(b)

45250

59922

74588

89254

(c)

Figure 15 AuNCsSiO2



2










Fluorescent imaging

Incubation for

24h or 48h


HAuCl4

h

Gold-nanocluster

Tumor

(a)

Scal

ed (c

ount

ss)

0

001(b) (c) (d)


4



4






Acknowledgments


References






























119909

Au25minus119909








8

















and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials




h998400 h998400

h h

H2O2

HRP-AuNCsHRP

(a)

0

100nM250nM500nM1120583M5120583M10120583M25120583M50120583M100120583M

400 450 500 550 600 650 700

0

50

100

150

200

250

300

350

FL in

tens

ity (a

u) 35

40

45

50

55

01 05 1 5 10

I 450l 4

50

120582 (nm)

[H2O2] (120583M)

(b)


O2






O2








Apt-Q AuNP

Apt-QAuNPPDGFs

Apt-QAuNP

PDGF receptor

FRET

FRET

FRET

h 998400h

h 998400h

h 998400h

PDGF receptor

(a)

(b)

(c)

AuNDPDGF AA-L

AuNPApt-Q



2

O2


2

O2





ApoptosisCyt C

Cellular uptake

Endosome


Mitochondria



2






25




50120583m

(a)

50120583m

(b)

50120583m

(c)

50120583m

(d)






2


2



2

O3


119881

1205733

integrin in U87


(a)

(b)

(d)

(e)

(c)

DN

A d

amag

e rat

e

0

20

40

60

80

100


(f)



O3


O3

Au (RGD-Gd2

O3





5000

19500

33000

46500

60000

(a)

25000

37500

50000

62500

75000

(b)

45250

59922

74588

89254

(c)

Figure 15 AuNCsSiO2



2










Fluorescent imaging

Incubation for

24h or 48h


HAuCl4

h

Gold-nanocluster

Tumor

(a)

Scal

ed (c

ount

ss)

0

001(b) (c) (d)


4



4






Acknowledgments


References






























119909

Au25minus119909








8

















and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials








Apt-Q AuNP

Apt-QAuNPPDGFs

Apt-QAuNP

PDGF receptor

FRET

FRET

FRET

h 998400h

h 998400h

h 998400h

PDGF receptor

(a)

(b)

(c)

AuNDPDGF AA-L

AuNPApt-Q



2

O2


2

O2





ApoptosisCyt C

Cellular uptake

Endosome


Mitochondria



2






25




50120583m

(a)

50120583m

(b)

50120583m

(c)

50120583m

(d)






2


2



2

O3


119881

1205733

integrin in U87


(a)

(b)

(d)

(e)

(c)

DN

A d

amag

e rat

e

0

20

40

60

80

100


(f)



O3


O3

Au (RGD-Gd2

O3





5000

19500

33000

46500

60000

(a)

25000

37500

50000

62500

75000

(b)

45250

59922

74588

89254

(c)

Figure 15 AuNCsSiO2



2










Fluorescent imaging

Incubation for

24h or 48h


HAuCl4

h

Gold-nanocluster

Tumor

(a)

Scal

ed (c

ount

ss)

0

001(b) (c) (d)


4



4






Acknowledgments


References






























119909

Au25minus119909








8

















and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials




ApoptosisCyt C

Cellular uptake

Endosome


Mitochondria



2






25




50120583m

(a)

50120583m

(b)

50120583m

(c)

50120583m

(d)






2


2



2

O3


119881

1205733

integrin in U87


(a)

(b)

(d)

(e)

(c)

DN

A d

amag

e rat

e

0

20

40

60

80

100


(f)



O3


O3

Au (RGD-Gd2

O3





5000

19500

33000

46500

60000

(a)

25000

37500

50000

62500

75000

(b)

45250

59922

74588

89254

(c)

Figure 15 AuNCsSiO2



2










Fluorescent imaging

Incubation for

24h or 48h


HAuCl4

h

Gold-nanocluster

Tumor

(a)

Scal

ed (c

ount

ss)

0

001(b) (c) (d)


4



4






Acknowledgments


References






























119909

Au25minus119909








8

















and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials




50120583m

(a)

50120583m

(b)

50120583m

(c)

50120583m

(d)






2


2



2

O3


119881

1205733

integrin in U87


(a)

(b)

(d)

(e)

(c)

DN

A d

amag

e rat

e

0

20

40

60

80

100


(f)



O3


O3

Au (RGD-Gd2

O3





5000

19500

33000

46500

60000

(a)

25000

37500

50000

62500

75000

(b)

45250

59922

74588

89254

(c)

Figure 15 AuNCsSiO2



2










Fluorescent imaging

Incubation for

24h or 48h


HAuCl4

h

Gold-nanocluster

Tumor

(a)

Scal

ed (c

ount

ss)

0

001(b) (c) (d)


4



4






Acknowledgments


References






























119909

Au25minus119909








8

















and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials




(a)

(b)

(d)

(e)

(c)

DN

A d

amag

e rat

e

0

20

40

60

80

100


(f)



O3


O3

Au (RGD-Gd2

O3





5000

19500

33000

46500

60000

(a)

25000

37500

50000

62500

75000

(b)

45250

59922

74588

89254

(c)

Figure 15 AuNCsSiO2



2










Fluorescent imaging

Incubation for

24h or 48h


HAuCl4

h

Gold-nanocluster

Tumor

(a)

Scal

ed (c

ount

ss)

0

001(b) (c) (d)


4



4






Acknowledgments


References






























119909

Au25minus119909








8

















and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials





5000

19500

33000

46500

60000

(a)

25000

37500

50000

62500

75000

(b)

45250

59922

74588

89254

(c)

Figure 15 AuNCsSiO2



2










Fluorescent imaging

Incubation for

24h or 48h


HAuCl4

h

Gold-nanocluster

Tumor

(a)

Scal

ed (c

ount

ss)

0

001(b) (c) (d)


4



4






Acknowledgments


References






























119909

Au25minus119909








8

















and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials




Fluorescent imaging

Incubation for

24h or 48h


HAuCl4

h

Gold-nanocluster

Tumor

(a)

Scal

ed (c

ount

ss)

0

001(b) (c) (d)


4



4






Acknowledgments


References






























119909

Au25minus119909








8

















and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials






























119909

Au25minus119909








8

















and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials














and Ag8




(SR)50

andAu130minus119909

Ag119909

(SR)50






































4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials
















4


10







25




25


11





P)14

Au39

C1198976

]C1198972



1198973

(PMe2

Ph)10

Cl2

](PF6

)3



[P(C6

H5

)3

]12

Cl6




20






25





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials





119899








15










(SC2

H4

Ph)24










2

O3








































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials

































































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials



review article fluorescent gold nanoclusters: synthesis and … · 2019. 7. 31. · fluorescent...

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