Poly(sodium-4-styrene)sulfonate-Iron Oxide Nanocomposite Dispersions with ControlledMagnetic Resonance Properties

Serena A. Corr,† Yurii K. Gun’ko,*,† Renata Tekoriute,† Carla J. Meledandri,‡ andDermot F. Brougham*,‡

School of Chemistry and CRANN Institute, Trinity College, UniVersity of Dublin, Dublin 2, Ireland, and NationalInstitute for Cellular Biotechnology, School of Chemical Sciences, Dublin City UniVersity, Dublin 9, Ireland

ReceiVed: June 23, 2008; ReVised Manuscript ReceiVed: July 29, 2008

We report synthesis and studies of magnetic suspensions with tunable low-field relaxivities. Using a one-stepprocedure, we have prepared magnetic fluids composed of polyelectrolyte stabilized magnetite nanoparticles.We have demonstrated the effect of varying the synthetic conditions, in particular, the iron and PSSSpolyelectrolyte content for a fixed polymer chain length, on the emergent magnetic resonance properties ofthe iron oxide nanoparticle suspensions. The new magnetic fluids have a potential for in vivo MRI diagnostics.

There are many reported methods for the preparation ofmagnetic nanoparticles of iron oxide.1 Water-stable magneticnanoparticle suspensions and corresponding magnetic fluids havewide-ranging biomedical applications as hyperthermic mediators,MRI contrast agents, and drug delivery systems.2 Biologicalpolyelectrolyte molecules (e.g., DNA) have been demonstratedto serve as excellent templates for the preparation of self-assembled nanostructured materials in recent years.3 Neverthe-less, controlling the formation and stability of the suspensionsis difficult as the complex microscopic events of nucleation andgrowth proceed far from equilibrium and these processes arestrongly influenced by the concentration and chemi- andphysisorption characteristics, including the charge of the poly-electrolyte and the ions. Previously, we reported the formationof ordered nanowires of magnetite nanoparticles on the backboneof single-stranded herring DNA and their alignment in amagnetic field.4 These nanowire-like assemblies also providedus with a stable magnetic fluid (see Scheme 1), which gaveunprecedented high relaxivity at low field. We believe magneticfluids of this type could have an important application as low-field MRI contrast agents.

Polymers are frequently used as stabilizers and cross-linkingagents in the preparation of magnetic nanoparticle assemblies.5

For example, controlled clustering of magnetic particles usingcationic-neutral block copolymers was reported for the prepa-ration of magnetic fluids with improved contrast for MRI.6

Random copolymers of acrylic acid, styrenesulfonic acid, andvinylsulfonic acid have been used to stabilize magnetic nano-particles and exert some control over the size of the resultingnanoclusters.7 Linear chains of magnetite nanoparticles have alsobeen prepared by using magnetic-field-induced self-assemblyof citrate stabilized magnetite, by using poly(2-vinyl-N-meth-ylpyridinium iodide) as the template.8 However, control overthe emergent magnetic properties of the nanocluster suspensions

continues to be crucial for the further development and MRIapplications of nanoparticle-based magnetic fluids.

With this in mind, we have prepared a new family of contrastagents using, instead of the biopolyelectrolyte DNA, com-mercially available polyelectrolytes to act as both nanocompositeassembly directors and water-stable surfactants. We recentlycommunicated the synthesis and in vivo MRI studies ofpoly(sodium-4-styrene) sulfonate (PSSS) stabilized magneticnanocomposite suspensions.9 We now report, for the first time,the effect of varying the synthetic conditions, in particular, theiron and PSSS polyelectrolyte content for a fixed polymer chainlength, on the emergent magnetic resonance properties of theiron oxide nanoparticle suspensions.

A predetermined mass of polyelectrolyte was dissolved inMillipore water (10 mL) to produce a library of magnetic fluids.Briefly, FeCl3 ·6H2O (1.1 g; 4 mmol) and FeCl2 ·4H2O (0.4 g;2 mmol) were dissolved in deoxygenated Millipore water (100mL). Aliquots of this solution were added to polyelectrolytesolutions according to Table 1. The solution was allowed tostir for 15 min before addition of ammonia solution. The

* To whom correspondence should be addressed. E-mail: igounko@tcd.ie (Y.K.G.); dermot.brougham@dcu.ie (D.F.B.).

† Trinity College.‡ School of Chemical Sciences.

TABLE 1: Reagent Ratios Used in This Study

sample [Fe] (×10-3 M) [PSSS] (×10-5M)Fe/PSSS polymer

(∼monomer)

Group IA 40 40.8 97.1(0.286)B 30 35.7 85.0(0.250)C 30 17.8 169(0.500)

Group IID 20 1.90 1019(3.00)E 30 1.43 2133(6.25)F 25 1.22 2039(6.00)G 20 0.92 2039(6.00)

Group IIIH 40 4.08 985.4(2.90)I 40 2.04 1937(5.70)J 40 0.82 4927(14.5)K 30 0.71 4248(12.5)

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2008, 112, 13324–13327

resulting precipitate was washed with Millipore water (5 × 10mL). The final, fifth washing was a stable aqueous suspensionwhich has been characterized by TEM (see Figure 1 forexamples) and NMRD analysis. The black precipitate was driedunder vacuum and analyzed by X-ray diffraction, IR, and Ramanspectroscopy. XRD patterns and Raman spectra collected forall samples confirm the formation of magnetite nanoparticles,with peaks at 680 and 496 cm-1 in the Raman spectra, in goodagreement with the literature values for magnetite.10 For allPSSS-functionalized nanoparticles, IR stretches for aromaticC-C bonds, CH2 groups, sulfonate bonds, and aromatic C-Hbonds are observed. A broad feature at 580 cm-1 is attributedto the Fe-O stretch, while a shoulder at 631 cm-1 is probablythe Fe-O-S bend. TEM images were analyzed to determinethe primary particle size; see Table 2.

For all of the Group I preparations (low Fe/PSSS ratio),significantly smaller (av. 6.9 nm) primary nanoparticle coreswere formed. On the other hand, when the ratio was higher,Groups II and III, the cores were larger (av. 9.9 nm). This ispresumably because of an increased number of nucleation sitesalong the polymer for Group I samples, for which the PSSSconcentration is higher, and hence a growth phase that isrestricted by the availability of iron. In addition, the higherconcentration of polyelectrolyte in the samples may result inbetter polymer coating of the initial nanoparticles, limitingfurther growth.

There was no significant difference, or trend, in the hydro-dynamic size as measured using photon correlation spectroscopybetween, or within, the three groups. In all cases, the suspensionshad Dhyd in the range of 100-200 nm, and for all of thesuspensions reported, the polydispersity indices were low, <0.2,confirming that the suspensions contained unimodal distributionsof relatively sized monodisperse clusters.

In most cases, aqueous suspensions were obtained that werestable for hours in the presence of static magnetic fields up to2 T and for periods of months in the absence of a magneticfield. The MRI potential of the stable suspensions was assessedby nuclear magnetic resonance dispersion (NMRD). NMRD isa technique where the frequency dependence of the relaxationrate of the suspending medium (water) is measured. In the caseof suspensions of superparamagnetic nanoparticles, the relax-ation rate enhancement is usually expressed as the concentration-independent spin-lattice relaxivity, r1, which has units of s-1

mM-1 (of Fe). The r1 values are critical as they measure thecontrast efficacy of the suspension for T1-weighted imagingapplications and provide information on the magnetic propertiesof the suspensions.

While the relaxivity values vary somewhat from sample tosample, in all cases, the relaxation enhancement is verysignificant, and the NMRD profiles exhibit an r1 maximum inthe range of 1-8 MHz, Figure 2, 3a. This demonstrates thatthe suspensions are predominantly superparamagnetic.11 TheNMRD experiments confirm that, as indicated in the syntheticscheme, the suspensions divide naturally into three groups; seeTable 2. For Group I, the r1 maxima are at high frequency (6-8MHz) and are comparatively broad (>20 MHz); the low-fieldplateaus occur at low r1 values (11-15 s-1 mM-1); see Figure2. As the NMRD profiles are very similar for this group, fewersuspensions were prepared. For Group II, the r1 maxima are atlower frequencies (2-3.5 MHz) and are less broad (12-16MHz); the low-field plateaus are at higher r1 values (15-32s-1 mM-1) and are more variable from suspension to suspension;see Figure 3a. For Group III, the r1 maxima are at the lowestfrequency (1-2 MHz) and are the narrowest observed (4-9MHz); the low-field plateaus are at elevated r1 values (>40 s-1

mM-1), Figure 3b, and, as was the case for Group II, but notGroup I, are more variable from suspension to suspension. Forall three groups, the ∆ν values show that, as expected, therelaxivity maxima cover almost 1.5 orders of magnitude infrequency (MHz scale).

The NMRD data conform well to the theory developed byMuller et al.11 for water relaxation by superparamagneticnanoparticles. The theory is strictly applicable to suspensionsof monodisperse, sub-20 nm particles, with uniaxial magnetoc-rystalline symmetry. The parameters of the model include thecore size, Dcore, the saturation magnetization, Ms, the magnetic

Figure 1. TEM images of samples (a) A, (b) G, and (c) J from GroupsI, II, and III, respectively. The scale bar corresponds to 20 nm.

TABLE 2: Properties of the Stable Aqueous Suspensionsa

sample Dcoreb (nm) r1plat (s-1 mM-1) νmax (MHz) ∆νc (MHz)

Group IA 6.5 ( 1.0 11.7 7.9B 7.1 ( 1.0 14.7 6.9 28C 7.0 ( 1.1 14.7 6.2 22

Group IID 10.2 ( 1.2 31.4 2.4 12E 10.1 ( 2.2 23.5 2.4 16F 9.4 ( 1.6 10.8 3.0 16G 7.9 ( 1.2 15.3 3.4 16

Group IIIH 11.2 ( 2.0 58.7 1.5 9I 10.3 ( 1.7 47.1 1.9 8J 9.8 ( 1.7 66.4 1.2 4K 9.9 ( 1.0 42.7 1.9 6

a The magnetic nanoparticle core size as estimated from TEManalysis, Dcore; the r1 value at low frequency, r1plat; the frequency atwhich the r1 maximum occurs, νmax; and the width at half-height ofthe r1 maximum, ∆ν. b Estimated from TEM. c Estimated width athalf-height of the r1 maximum.

Figure 2. NMRD profiles for the Group I samples A (9), B (4), andC (O). The solid line is a simulation for a SPM dispersion with Dcore

) 12 nm, ∆Eanis ) 1 GHz, and Ms ) 49 emu ·g-1. All measurementswere carried out at 25 °C ( 1 °C, with a measuring frequency of 9.25MHz, on a Stelar FFC2000.

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anisotropy energy, ∆Eanis (expressed in frequency units), andthe Neel correlation time, τN. Given the assumptions of themodel and the large number of parameters required, furtherextension of the theory to account for size-disperse suspensionsis not appropriate. For the samples presented, the profiles canbe reasonably simulated with fixed core diameters of 12 nmfor Group I and 16 nm for Groups II and III, which suggeststhat the samples are sufficiently monodisperse in this case forthe theory to be validly applied.

Small systematic overestimations of Dcore from SPM simula-tions have been observed before.12 This effect and the deviationof the simulations from the data on the low-frequency side of

the r1 maximum probably arise from the approximate way inwhich the magnetic crystals are treated in the theory; it isassumed that (i) they have uniaxial magnetocrystalline symmetryand (ii) the motion of the moments can be well-represented bya single correlation time, τN, irrespective of the electronic spinenergy level.

These limitations do not invalidate the analysis of themagnetic properties derived from the simulations; the NMRanalysis reproduces the variation in particle size, observed byTEM, between the low- and high-ratio preparations. The valuesobtained for τN range from 10 to 16 ns, as expected.11 Finally,we find Ms in the range of 30-50 emu ·g-1, which is theexpected range for Fe3O4 nanoparticles of this size.13 Thequantitative agreement of these parameters validates our inter-pretation that the increased low-field relaxivity arises fromincreased magnetic anisotropy energy for the Group II and, inparticular, the Group III suspensions; see Figure 3b.

Increased magnetocrystalline anisotropy can arise from thestructure of the crystals and/or from interactions between crystalswithin the polyelectrolyte-stabilized clusters. Given the unifor-mity of the size and magnetization of the crystals, and the factthat anisotropy energies of <2 GHz are expected for isolatedsuperparamagnetic particles in this size range,11 it is reasonableto assign the increased anisotropy to interparticle interactionswithin the clusters. The increased relaxivity observed for GroupIII compared to that for Group II can therefore be interpretedas arising from stronger or more numerous interparticle interac-tions. This is consistent with an increased density of nucleationsites along the polymer during the reaction for Group III wherethe iron concentration is higher and, hence, increased interpar-ticle interactions in the resulting nanocomposites. Although, asalready noted, both groups undergo comparable growth phasesresulting in very similar primary particle sizes.

The standard SPM theory has been expanded to includemagnetic clusters of superparamagnetic iron oxide (SPIO)14 byconsidering the residence time of the water within a given clusteras analogous to a chemical exchange model. This approach hasbeen shown to reproduce the changes in spin-lattice relaxivityobserved for chemically induced flocculation of dextran-stabilized magnetic nanoparticles, the agglomeration of whichresulted in gradual suppression and broadening of the r1

maximum. This situation is consistent with an increased waterresidence time in the larger clusters, where the relaxationcontribution from any given core within the agglomerate is takento be superparamagnetic. For the materials that we present here,the physical situation is quite different; increased low-fieldrelaxivity is observed, which can be simulated using the standardSPM theory assuming a progressively greater magnetic anisot-ropy energy. The value obtained for ∆Eanis for the SPM-typedispersions, Group I, of 1 GHz corresponds to ∼6KBT at 295K.Values of 2-4 GHz observed for Group II are thereforeconsistent with the onset of blocking, which is even moreimportant for Group III. For the suspensions that exhibit veryhigh relaxivity, the SPM approach begins to lose validity, as inthe case of sample J for which it was difficult to simulate theprofile, as more and more of the magnetism is blocked. Wehave previously4 reported partial magnetic blocking for linearassemblies of iron oxide nanoparticles stabilized with herringDNA. In particular, for suspensions stabilized with substantiallysingle-stranded DNA, the interparticle interactions were stronger,as expected, and the profiles did not conform to SPM theory.Instead, they exhibited power law dependence of r1 onfrequency, with no low-frequency plateau evident. Similar

Figure 3. (a) NMRD profiles for the Group II samples D (O), E (0),F (∆), and G()) and those for the Group III samples H (9), I(2), J(1), and K (b). The solid curves are simulations using the standardsuperparamagnetic theory,11 with Dcore ) 16 nm. (b) The dependenceof the low-frequency relaxivity on the magnetic anisotropy energy. Thevalues are taken from the simulations presented in Figures 2 and 3afor the Group I (0), Group II (O), and Group III (∆) samples.

SCHEME 1: Preparation of the PSSS-StabilizedMagnetite Nanoparticlesa

a Solutions of the iron salts are mixed with the polyelectrolyte and,upon addition of ammonia and following subsequent washings, afforda stable magnetic fluid.

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behavior has been noted for other complex aggregated magneticmaterials, such as core-shell iron-iron oxide nanoparticleclusters.15

In conclusion, our approach allows preparation of stableaqueous magnetic fluids in a single-step procedure. We haveused it to produce a library of magnetic suspensions, whoseproperties reflect the effect of the conditions used on the pa-rameters of nanocomposite formation. The method has advan-tages over other procedures in that it is a quick, inexpensive,one-step experiment which is highly reproducible and whoseparameters can be varied to produce magnetic fluids with tunablelow-field relaxivities.

Acknowledgment. We would like to thank Alain Roch andRobert Muller for making their programme publically available.This work was supported by the Science Foundation IrelandRFP Grant (05/RFP/CHE0103) and Enterprise Ireland Proof ofConcept Fund (PC/2004/429).

References and Notes

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