nanomaterials in biomedical application
TRANSCRIPT
NANOMATERIALS IN BIOMEDICAL APPLICATION
By:Sumeet Sharma
M.Tech- Materials EngineeringEmail- [email protected]
Department of Metallurgical and Materials EngineeringVisvesvaraya National Institute of Technology, Nagpur, Maharashtra
WHAT ARE NANOMATERIALS AND NANOPARTICLES??
• one external dimension in the size range from approximately 1-100 nanometers
• Nanoparticles are objects with all three external dimensions at the nanoscale
CLASSIFICATI0N OF NANOMATERIALS:
Fig1:Schematic classification of nanomaterials (a)3D (b)2D (c)1D (d)0D
(a) (b) (c) (d)
Source:V.Pokropivny,R.Lohmus,I.Hassainova,A.Pokropinvy;Introduction in nanomaterials and nanotech.;Univ. of TARTU,2007,225p.
Some common terms in nanomaterials
• Nanoshells are nanoparticles that consist of an inner core of one type of material and an outer layer of another only a few nanometers thick.(fig 2(a))
NANOSHELLS
QUANTUM DOTS• Quantum dots are tiny particles, or
“nanoparticles”, of a semiconductor material, traditionally chalcogenides (selenides or sulfides) of metals like cadmium or zinc (for example CdSe or ZnS), which range from 2 to 10 nanometers in diameter(fig 2(b))
Fig 2(a) model of gold Nanoshell
Fig 2(b) Quantum dots
Imaging method…
Confocal microscopy• light is incident on a molecule, it may absorb the light and then emit light
of a different color, a process known as fluorescence.
Fig 3 showing confocal microscopy(a) shows mechanism of flourescence (b) shows rejection of light not incident on focal plane (c) shows basic setup of confocal microscopy
Source:confocal microscopy,Denis Semwogerere;Eric R.Weeks,Emory Univ.,Atlanta,Georgia,USA
(a)
(b)
(c)
Biomedical applications of nanomaterials• Biological imaging using quantum dots• Immuno flouroscent biomarker imaging• Target specific flouroscent imaging• Immunogold labelling• Targeted drug delivery using nanoparticles• Gold nanoshells for immunoassay and cancer
detection and therapy• A carbon nanotube field emission multipixel x-ray
array source for microradiotherapy application
Biomedical applications of nanomaterials …
Biological imaging using quantum dots• In vivo targeting ZnS capped CdSe quantum dots
coated with lung targeting peptide via Thiol exchange reaction accumulate in the lungs of mice.
• These ZnS capped CdSe QDs emit under green and red light 550nm and 625nm flouroscence maxima,respectively.
Source: Ackerman M.E.,W.C.W. Chan,P.leakkemen,PKAS,99(2002
Fig. 4 In vivo target imaging using ZnS capped CdSe QDs(a) With lung targeting peptides(b) With peptides and PEG
(a) (b)
Fig. 5 Image as under flouroscent microscope
Biomedical applications of nanomaterials …
Source: Synthesis of ternary CuInS2/ZnS quantum dot bioconjugates and their applications for targeted cancer bioimagingDOI: 10.1039/B916663G
• These QDs were injected into tail vein of mice ,it was then it was frozen sectioned and examined under an inverted flouroscent microscope or confocal microscope• Adding polyethylene glycol [PEG] to quantum dots prevents non selective accumulation of QDs in reticuloendothelial tissues.
Biomedical applications of nanomaterials …
Immuno flouroscent biomarker imaging• QD can be used as core shell with antibodies
anchored to it,for ex.CdSe-ZnS capped with polyethylene glycol(PEG) this is termed as QD-PEG
• PSMA is known biomarker for diagnostic and therapeutic applications in prostate cancer
Biomedical applications of nanomaterials …
Target specific flouroscent imaging• Antibody of prostrate selective membrane antigen (PSMA-Ab)
is anchored.Target molecule is antigen present in cell membrane
• PSMA is only present in cell membrane of a prostrate cancer cell(C4-2)
QD
Fig 6:mechanism of site specific flouroscent imaging
Biomedical applications of nanomaterials …
Anchor biomolecule
Target biomolecule
Bio-conjugateInoragnic nanoparticle
Fig 7: Hybridization of conjugate biomolecules on inorganic nanoparticle surface
Source: Nisman R.,G. Dellaire,Y.Ren,R.Li,Cytochem.,52(2004),p.p. 13-18
Mechanism-Hybridization of antibody on the nanoparticle surface with the antigen present on the cell wall of cancer cell - bioconjugate formation (fig 3 )
Biomedical applications of nanomaterials …
3 cases
Flouroscent staining happens(fig5: (a))
Reason:presence of antigen containing cancer cell and antibody capped nanoparticles(QD-PSMA)
QDs doesnot attach to cell wall surface(fig5: (b))
Reason: QDs are not anchored with antibody
QDs doesnot attach tocell wall surface even though they are anchored with antibody(fig 5: (c))
Reason: absence of target antigen cell wall or non-cancerous PC-3 cells
Target specificity
Biomedical applications of nanomaterials …
Fig 8:Prostate specific membrane antigen (PSMA) targeted nanoparticles for imaging and therapy of prostate cancer
Source: Sachin S. Channdran,Sangeeta Ray,Martin G.Pomper, Pub.no.US20110200677 A1
Fig 9: Various interactions of QDs
Flouroscence image
Brightfield image QD-PSMA with C4-2 cancer cell
Brightfield image
Brightfield image
QD-PEG with C4-2 cells QD-PSMA with PC-3 Cells
Flouroscence image(negative staining)
Flouroscence image(negative staining)
(a) QD-PSMA with C4-2 cancer cell (b) (c)
Source: Nisman R.,G. Dellaire,Y.Ren,R.Li,Cytochem.,52(2004),p.p. 13-18
Biomedical applications of nanomaterials …
Immunogold labellingGold particles Immuno targetted Immunogold
Gold particles are used as labels for imaging cell lines and tissues
• Immunoglobulin 1g G-capped Gold nanoparticles used for imaging pathogenic organisms like staphyloccocus aureus,staphyloccocus pyrogenes,staphyloccocus saprophyticus.
• 1g G can bind specifically to pathogens produced by Bacteria , thus it is used to image Bacteria by TEM
• No labelling when citrate capped and BSA-capped gold nanoparticles are used
Fig 10: TEM image of Staphyloccocus Saprophyticus by incubating these bacteria with Au-1g G-nanoparticle
Source: C.W. Chan,S.Nie,Science,281(1999),pp. 2016-18
Biomedical applications of nanomaterials …
Fig 11: (a)(b)(c)(d) high reflectance confocal images of SiHa cells labelled with anti EGFR/Au conjugates.(e)(f)Nonspecific labelling using Au conjugates with BSA
Laser scanning confocal reflectance
Combined confocal reflectance/transmittance
(a)
(c)
(e)
(b)
(d)
(f)
Biomedical applications of nanomaterials …
Targeted drug delivery using nanoparticles• Slow and selective release of drugs to the targeted organs• 2 kinds of nanomaterials used: (1)organic (2)organo-inorganic hybridEx:Antibacterial activity of Vancomycin capped Au nanoparticles Imp: minimum inhibitory concentration was lower (1/50 of pure vancomycin) Efficiently binds with bacteria Also acts against vancomycin resistant E.Coli bacteria
Fig 12:TEM image of E.Coli being treated by Au@van
Au@van
Source:Gu H.,P.L.Ho,E.Tong,L.Wang,B. Xu;Nano. Letter,3(2003,pp.1261-3)
Biomedical applications of nanomaterials …
Composite nanoparticles for treatment of cancer1. Use of magnetic nnoparticles carrying active drugs,for ex:anticancer drug
mitoxantrone adsorbed to magnetic iron oxide nanoparticles which were held together and stabilized by dextran matrix,addition of responsive component like Au nanoparticles can further help to trigger release of anticancer drug locally by photoinduced heating.
(Sources: (1)Alextou C.,Arnold W.,Klein R.J.;A.S. Locoregional cancer treatment with magnetic drug trgetting,cancer res.2000,60,6641-6648(2)Skirtach A.G.,Munoz-Javler A.,Kreft O.,Kohler K.,Laser induced release of encapsulated materials inside liing cells,Angew. Chem.,int. ed. 2006,45,4612-4617)
2. Local heat generation by optical excitation of gold nanoparticles can destroy tumor cells,this therapy is called hyperthermia
(Jain R.K.,Transport of molecules,particles and cells in solid tumors,ann.rev. Blomed.eng.,1999,1,241-263)
3. Microwave irradiation of magnetic and gold nanoparticles,destrot tumor cells by heat
(Pankhurst Q.A.,Conolly J.,Jones S.K.,Applications of magnetic nanoparticles in Biomedicine.J.Phys.D:Appl.Phys.,2003,36,R167-R181)
4. Photodyanamic therapy making use of photosensitizing molecules(porphyrins) as active components,which are activated by light(near IR region),releasing reactive Oxygen species(ROS),which cause tumor regression
(Bakloa R.,Ohba H.,Zhelev Z.,Ishikawa M.;Quantum dots as Photosnsitizers,Nat.Biotechnol.,2004,22,1360-1361)
Special Thanks to- Dr. J..G. Bhatt for his guidance and suggestions
• Thanking you