DOI: 10.1021/la903513v 4465Langmuir 2010, 26(6), 4465–4472 Published on Web 12/01/2009

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© 2009 American Chemical Society

Optimized Steric Stabilization of Aqueous Ferrofluids andMagnetic Nanoparticles

Nirmesh Jain,† Yanjun Wang,† Stephen K. Jones,‡ Brian S. Hawkett,*,† andGregory G. Warr†

†School of Chemistry and Key Centre for Polymers and Colloids, The University of Sydney, NSW 2006,Australia, and ‡Sirtex Medical Limited, Sydney, NSW, Australia

Received September 17, 2009. Revised Manuscript Received October 28, 2009

The preparation and properties of an aqueous ferrofluid consisting of a concentrated (>65 wt %) dispersion ofsterically stabilized superparamagnetic, iron oxide (maghemite) nanoparticles stable for several months at high ionicstrength and over a broad pH range is described. The 6-8 nm diameter nanoparticles are individually coated with ashort poly(acrylic acid)-b-poly(acrylamide) copolymer, designed to form the thinnest possible steric stabilizing layerwhile remaining strongly attached to the iron oxide surface over a wide range of nanoparticle concentrations.Thermogravimetric analysis yields an iron oxide content of 76 wt % in the dried particles, consistent with a drypolymer coating of approximately 1 nm in thickness, while the poly(acrylamide) chain length indicated by electrospraymass spectrometry is consistent with the 4-5 nm increase in the hydrodynamic radius observed by light scattering whenthe poly(acrylamide) stabilizing chains are solvated. Saturation magnetization experiments indicate nonmagneticsurface layers resulting from the strong chemical attachment of the poly(acrylic acid) block to the particle surface, alsoobserved by Fourier transform infrared spectroscopy.

Introduction

Ferrofluids are colloidal dispersions of small, single-domainmagnetic particles suspended in a continuous phase. Ferrofluidscharacteristically have bothmagnetic and fluid properties and havefound a diverse range of applications in various fields of biologyand medicine, such as enzyme and protein immobilization, radio-pharmaceuticals, magnetic resonance imaging, diagnostics, immuno-assays, purification, separation, and controlled drug release.1-5

Although well-dispersed magnetic nanoparticles can be ob-tained by ball milling,6 the high-energy requirements and un-avoidable contamination of the product have necessitated thedevelopment of more economical and reliable ways to producemagnetic particles by chemical coprecipitation. A variety ofsynthetic routes to stable nanoparticle dispersions of iron oxide(γ-Fe2O3), the dominant magnetic material in magnetic fluidpreparations, have been developed involving coprecipitation ofFe(II) and Fe(III) salts with base and addition of adsorbingstabilizers. Magnetic fluids may be stabilized in oil or water byanionic or nonionic surfactants as dispersing agents,7-9 andMassart and co-workers have obtained stable aqueous alkaline

and acidicmagnetic liquids by free precipitation.10,11 Shimoiizakaet al.12 developed bilayer stabilization in the early 1980s by firstprecipitating oleic-acid-coated particles and then redispersingthem in aqueous solutions of sodium dodecylbenzene sulfo-nate, poly(oxyethylene) nonylphenyl ethers, and di(2-ethylhexyl)-adipate, which adsorb as a second layer on top of the oleic acid.Wooding et al.13 subsequently produced stable aqueous magneticfluids using saturated and unsaturated fatty acids as primary andsecondary surfactants. Highly crystalline and monodisperse ma-ghemite (γ-Fe2O3) nanocrystallites have recently been reported inoil from the thermal decomposition of a metal-oleate complex inthe presence of oleic acid,14,15 which can then be transferred intoan aqueous medium using phase transfer reagents.16

The uses of magnetic nanoparticle dispersions stabilized en-tirely by electrostatic repulsion or surfactant bilayers are re-stricted by their sensitivity to conditions such as pH and ionicstrength, and offer little flexibility for changing the surfaceproperties of the particles. This is especially important in bio-logical applications, where these particles are to be administeredinto a living organism and need to be very stable at both neutralpH and high ionic strength. The stabilization of magnetic nano-particles for these environments can be achieved by coating theparticle surface with organic polymeric materials/surfactants thatprovide steric repulsion between particles due to a combination ofelastic and osmotic effects.7,17

*To whom correspondence should be addressed. E-mail: b.hawkett@chem.usyd.edu.au.(1) Hafeli, U.; Schutt, W.; Teller, J.; Zborowski, M. Scientific and Clinic

Applications of Magnetic Carriers; Plenum: New York, 1997.(2) Weissleder, R.; Bogdanov, A.; Nuwelt, E. A.; Papisov, M. Adv. Drug

Delivery Rev. 1995, 16, 321.(3) Jordan, A.; Scholz, R.; Wust, P.; Schirra, H. J. Magn. Magn. Mater. 1999,

194, 185.(4) Kim, D. M.; Mikhaylova, M.; Wang, F. H.; Kehr, J.; Bjelke, B.; Zhang, Y.;

Tsakalakos, T.; Muhammed, M. Chem. Mater. 2003, 15, 4343.(5) Laurent, S.; Forge, D.; Port, M.; Roch, Alain, Robic, C.; Elst, L. V.; Muller,

R. N. Chem. Rev. 2008, 108, 2064.(6) Khalafalla, S. E.; Reimers, G. W. IEEE Trans. Magn. 1980,Mag-16(2), 178.(7) Berkovsky, B. M.; Medvedev, V. F.; Krakov, M. S. Magnetic Fluids:

Engineering Applications; Oxford University Press: New York, 1993.(8) Rosensweig, R. E. Ferrohydrodynamics; Cambridge University Press:

New York, 1985.(9) Kang, Y. S.; Risbud, S.; Rabolt, J. F.; Stroeve, P. Chem. Mater. 1996, 8,

2209.(10) Massart, R. IEEE Trans. Magn. 1981, Mag-17(2), 1247.

(11) Massart, R.; Dubois, E.; Cabuil, V.; Hasmonay, E. J. Magn. Magn. Mater.1995, 149, 1.

(12) Shimoiizaka, J. N. K.; Fujita, T.; Kounosu, A. IEEE Trans. Magn. 1980,Mag-16(2), 368.

(13) Wooding, A; Kilner, M.; Lambrick, D. B. J. Colloid Interface Sci. 1991,144, 236.

(14) Hyeon, T.; Lee, S. S.; Park, J.; Chung, Y.;Na,H. B. J. Am.Chem. Soc. 2001,123, 12798.

(15) Park, J.; An, K.; Hwang, Y.; Park, J.-G.; Noh, H.-J.; Kim, J.-Y.; Park,J.-H.; Hwang, N.-M.; Hyeon, T. Nat. Mater. 2004, 3, 891.

(16) Euliss, L. E.; Grancharov, S. G.; O’Brien, S.; Deming, T. J.; Stucky, G. D.;Murray, C. B.; Held, G. A. Nano Lett. 2003, 3, 1489.

(17) Hiemenz, P. C. Principles of Colloid and Surface Chemistry, 3rd ed.; Dekker:New York, 1997.

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Recently, a number of aqueous magnetic nanoparticle disper-sions have been reported using high molecular weight polymerssuch as dextran (MW=40000 g/mol), polyvinyl alcohol (MW=30-70000 g/mol), and so on as steric stabilizers and polymertemplates, but all have either failed the test of long-term stability,pH or electrolyte tolerance, or have not been demonstrated to besufficiently concentrated to form a true ferrofluid (i.e., >1017

particles/mL).18-23 Many of the polymeric stabilizers reportedonly bind weakly to nanoparticle surfaces and eventually desorbor exchange with bulk solution, compromising the long-termstability of the resultant dispersions.23

Nanoparticle dispersions at high iron oxide concentrations arebecoming important for biomedical applications such as hyper-thermia,5 but there are no reports available in literature to dateon sterically stabilized ferrofluids of iron oxide nanoparticlesat high concentrations (i.e., 50 wt % or more). The highest ironoxide contents achieved in the dried powder state is about 70wt%by Lee et al.,24 using a 66000 molecular weight random copoly-mer of (trimethoxysilyl)propyl methacrylate and polyethyleneglycol methacrylate. Iron oxide of 35 wt % has been reportedfor nanoparticles stabilized with natural polysaccharides such asdextran,25 and Harris et al.23 found 6.9-45.4 wt % magnetite innanoparticles coatedwith poly(ethylene oxide-b-urethane-b-ethy-lene oxide) of varying molecular weights (2690-13410 g/mol).None of these reports have demonstrated whether a ferrofluidcould be prepared from these sterically stabilized magneticnanoparticles, focusing instead on dilute dispersions or solidmagnetic nanoparticles.

The iron oxide concentration in sterically stabilized nano-particles either in its dry form or in the ferrofluid dispersion canhowever be maximized by reducing the thickness of the coating,that is, the lengthor themolecularweight of the steric stabilizer, toa minimum. Also, the use of short chain steric stabilizers ratherthan natural or synthetic long chain polymers is expected to yielda dispersion comprising individually coated small nanoparticles,rather than clusters, which is preferable in several biomedicalareas such as in magnetic resonance imaging (MRI).5 Aquil andco-workers26 have recently reported work in this direction, wherethey have investigated steric stabilization of iron oxide nano-particles by pH and temperature responsive block copolymers ofacrylic acid and N-isopropylacrylamide. Dilute nanoparticledispersions showed good stability in phosphate buffer solutions;however, the block lengths used were quite large (i.e., 60 acrylicacid units and 97-239 N-isopropylacrylamide units). This maylimit high concentrations of iron oxide achievable in their disper-sions or in the dry form, not mentioned in their work.

In this study, we present a novel and simple procedure for thesynthesis of an extremely stable, water-based γ-Fe2O3 ferrofluidvia coprecipitation followed by stabilization using a very shortchain, water-soluble diblock copolymer of acrylic acid andacrylamide prepared by reversible addition-fragmentation chain

transfer (RAFT) controlled radical polymerization. RAFT per-mits the steric stabilizing layer to be designed and optimized to beas thin as possible while remaining strongly attached to thenanoparticle surface under extremely challenging solution condi-tions. Using this approach, we demonstrate for the first time anaqueous ferrofluid in high electrolyte concentrations. The indivi-dual iron oxide nanoparticles retain their steric stabilization overa wide range of particle concentrations, at high aqueous electro-lyte concentrations, and over a broad pH range.

Materials and Methods

Fe(II) chloride tetrahydrate (99%) and Fe(III) chloride hexa-hydrate (98%) were purchased from Sigma-Aldrich and used assupplied. Fe(III) nitrate nonahydrate (99%) was from Merck(Germany) and used as supplied. Sodium citrate was of analyticalgrade and used without further purification. Ammonium hydro-xide (28% NH3 in water, w/w) was purchased from Ajax Fine-chem. Milli-Q water was used throughout the work. Acrylamide(AAM, 97%) was purchased from Sigma-Aldrich and used assupplied. Acrylic acid (AA, >99%) was purchased from Merckand distilled under reduced pressure prior to use. The RAFTagent 2-{[butylsulfanyl)carbonothioyl]-sulfanyl}propanoic acid(Scheme 1) was synthesized as described previously.27

Synthesis of Poly(acrylic acid)-block-Poly(acrylamide)Copolymer. Block copolymers with a variety of acrylic acidand acrylamide block lengths in a narrow distribution are readilysynthesized by RAFT as described below. In a typical reaction,acrylamide (4.47 g, 62.7 mmol), V-501 (0.04 g, 0.17 mmol), andRAFT agent (0.75 g, 3.15 mmol) were added to a 100 mL round-bottom flask containing amixture of dioxane 15 g andwater 7.5 g.The mixture was first heated at 70 �C for 2 h under a nitrogenatmosphere and then cooled to room temperature. Acrylic acid(2.2 g, 31.6mmol) andV-501 (0.04 g, 0.16mmol) were added, andthe reaction mixture was heated for another 2 h at 70 �C undernitrogen. At the end of this step, poly(acrylic acid)-b-poly-(acrylamide) copolymer was formed. The molecular weights ofthe initial poly(acrylamide) homopolymer and final copolymerwere determined by mass spectrometry, and a representativeexample is shown in Figure 1. Poly(acrylamide) mass spectrawere obtained by electrospray ionization on a ThermoQuestFinnigan LCQDecamass spectrometer. Copolymer spectra wereobtained from a Micromass (Waters) TofSpec-2e MALDI-TOFinstrument with a nitrogen laser (337 nm). Indole acrylic acid wasused as the matrix.

The electrospray mass spectrum of a typical poly(acrylamide)block (Figure 1A) revealed an average of approximately 14acrylamide units in each chain. The molecular mass of the blockcopolymer, determined byMALDI-TOFmass spectrometry, wascentered around 1951 g/mol. Based on an average of 14 acryla-mideunits in eachpoly(acrylamide) block, this indicates that therewere approximately 10 acrylic acid units in each poly(acrylic acid)block of the copolymer. The structure of the average copolymer,in this case AA10-b-AM14, is shown in Scheme 2.

Synthesis of the Sterically Stabilized Ferrofluids. Anumber of different batches of magnetic nanoparticles were

Scheme 1

(18) Pardoe, H.; Chua-Anusorn, W.; Pierre, T. G.; Dobson, J. J. Magn. Magn.Mater. 2001, 225, 41.(19) Mendenhall, G. D.; Geng, Y.; Hwang, J. J. Colloid Interface Sci. 1996, 184,

519.(20) Lee, J.; Isobe, T.; Senna, M. J. Colloid Interface Sci. 1996, 177, 490.(21) Ding, X. B.; Sun, Z.H.;Wan, G. X.; Jiang, Y. Y.React. Funct. Polym. 1998,

38, 11.(22) Underhill, R. S.; Liu, G. Chem. Mater. 2000, 12, 2082.(23) Harris, L. A.; Goff, J. D.; Carmichael, A. Y.; Riffle, J. S.; Harburn, J. J.;

Saunder, S, M. Chem. Mater. 2003, 15, 1367.(24) Lee, H.; Lee, E.; Kim,D.K.; Jang,N.K.; Jeong, Y. Y.; Jon, S. J. Am. Chem.

Soc. 2006, 128, 7383.(25) Pouliquen, D.; Le Jeune, J. J.; Perdisot, R.; Ermias, A.; Jallet, P. Magn.

Reson. Imaging 1991, 9, 275.(26) Aqil, A.; Vasseur, S.; Duguet, E.; Passirani, C.; Benoit,; J�erome, R.; J�erome,

C. J. Mater. Chem. 2008, 18, 3352.(27) Ferguson, C. J.; Hughes, R. J.; Pham, B. T. T.; Hawkett, B. S.; Gilbert,

R. G.; Serelis, A. K.; Such, C. H. Macromolecules 2002, 35, 9243.

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Jain et al. Article

synthesized during the course of this study.Variations in synthesisconditions such a stirring speed and scale of reaction result innanoparticles of slightly different size and polydispersity. Atypical synthesis is described below.

Nanoparticles were first prepared by chemical coprecipita-tion.10 In a typical reaction, 80 mL of 2 M FeCl3 3 6H2O in 1 MHCl and 40 mL of 2 M FeCl2 3 4H2O in 1 MHCl were mixed in a2 L beaker, and themixture diluted to 1.2 LwithMilli-Q water. Atotal of 250 mL ofNH4OH (28% (w/w)) was then quickly added,and the mixture vigorously stirred for 30 min. Upon addingNH4OH, the color of the mixture immediately turned fromorange to black due to formation of magnetite. Magnetite wasthen oxidized in acidic medium tomaghemite by heating at 90 �Cwith iron(III) nitrate for about 1 h. The color of the suspensionchanged from black to reddish brown. Maghemite particles werethen magnetically decanted, washed with acetone, and finallydispersed in water, yielding a stable dispersion. The pH of thedispersion was about 1.5-2, which was then raised to 5 by add-ing 0.3 wt % NaOH solution.

A1wt%solutionofAA10-b-AM14alsoatpH5was thenaddedto a 1 wt % dispersion of iron oxide maintained at the same pH.The mixture was vigorously stirred for 2 h at room temperature.At this pH, the copolymer was partially neutralized while thenanoparticles were sufficiently above their point of zero charge toalso be stable. Carboxylate ions from the acrylic acid block of thecopolymer chemically adsorbed onto the particle surface, yieldinga stable sterically stabilized dispersion of nanoparticles in water.

The dispersionwas then dialyzed to remove salt and any unboundpolymer. Larger particles created by aggregation during prepara-tion and stabilization in the dispersion were removed by ultra-centrifugation.

A reference electrostatically stabilized ferrofluid11 was pre-pared by heating the bare acidic ferrofluid described above to90 �C in an oil bath for about 1 h with the addition of sodiumcitrate solution (3 wt%, 50mL). Nanoparticles were precipitatedby adding acetone and sedimented using a strong magnet. Thesupernatant solution was decanted, and the wet cake of nano-particles thus obtainedwas redispersed inwater and then dialyzedagainst 20mM sodium citrate solution to remove salts and excesssodium citrate.

Characterization ofMagnetic Nanoparticles. The size andthe morphology of nanoparticles were investigated by transmis-sion electron microscopy (TEM, Philips CM120 Biofilter). Theferrofluid dispersions were first diluted in deionized water andthen deposited on a carbon-coated grid.

The sizedistributionof thenanoparticleswasmeasuredby laserlight scattering (Malvern Zeta Sizer 3000H) at 25 �C. The ferro-fluid dispersions were diluted to 0.1 wt%andmeasured at severalpH and salt concentrations. Size distributions as a function of pHand salt concentrations indicated a high degree of stability forthese dispersions.

Thermogravimetric analysis (TGA) of dried samples wascarried out using a TA Instruments TGA apparatus under aninert atmosphere at a heating rate of 5 �C/min up to 800 �C.

Fourier transform infrared (FTIR) spectra of dry powders ofthe neat copolymer and coatedmaghemite particleswere acquiredusing a Bruker IFS66 V FTIR spectrometer (Bruker, Karlsruhe,Germany)

X-ray diffraction (XRD) studies of powder samples wereperformed on a Shimadzu D-6000 diffractometer (40 kV,30 mA, divergence and antiscatter slits 1 mm, receiver anddetector slits 0.3 mm) to investigate the crystal structure of thebulkmaterial. TheX-ray diffraction patterns were taken from 10�to 70� (2θ value) using Cu KR radiation (λ = 1.5406 A).

Magnetic properties of the samples were measured in the solidstate at room temperature using a Lake Shore 7300 vibratingsample magnetometer (VSM) with a 2 T electromagnet. Themagnetic moment of each dried sample was measured overa range of applied fields from -20 to þ20 kOe with a sensitivityof 0.1 emu. The saturation magnetization was obtained by fittingthe experimental data to the Langevin equation.28

Results and Discussion

Ferrofluid. A typical ferrofluid is a stable dispersion of singledomain iron oxide nanoparticles (3-15 nm) coated with a thinlayer of a stabilizer in a liquid carrier. The fluid contains about1017 particles/mL and is opaque to visible light.8 It is welldocumented in literature8 that superparamagnetic nanoparticlesspike in a magnetic field due to induced dipoles in the nanopar-ticles aligning in the direction of the applied magnetic field,resulting in the spiking of the ferrofluid. This feature can onlybe observed at or above a certain threshold concentration ofmagnetic nanoparticles typically beyond 10 vol %. Figure 2demonstrates the characteristic spiking behavior exhibited byan AA10-b-AM14-coated, sterically stabilized aqueous ferrofluidin 2 M NaCl in a static magnetic field. Similar behavior is seenover a wide electrolyte concentration range and also in concen-trated ammonium salts. The ferrofluid remains well-dispersed forseveral months. To the best of our knowledge, no aqueous,sterically stabilized ferrofluid that spikes in a magnetic field haspreviously been reported. Nor is there any reported sterically

Figure 1. (A) Electrospraymass spectrumof the poly(acrylamide)block and (B)MALDI-TOFmass spectrumof theAA10-b-AAM14

block copolymer.

Scheme 2

(28) Berkowitz, A. E.; Lahut, J. A.; Vanburen, C. E. IEEE Trans. Magn. 1978,Mag-16, 184.

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stabilized ferrofluid exceeding the threshold concentration of 1017

particles/mL.8

A recent review5 noted that, despite considerable researcheffort on the coating of magnetic nanoparticles by monomericor polymeric materials, the process had yet to be optimized forsimplicity and effectiveness in preventing aggregation and sedi-mentation of magnetic nanoparticles. This work demonstrates avery simple and reproducible way of stabilizing magnetic ironoxide particles with a very thin layer formed by a short, water-soluble diblock copolymerof acrylic acid and acrylamide, yieldingsterically stabilized ferrofluids with very highmaximumdispersedphase concentrations (up to 65 wt % or an average number of8 � 1017 particles/mL, assuming an average core size of 7 nm).

Magnetic nanoparticle dispersions reported previously havebeen stabilized using a variety of biocompatible natural andsynthetic polymers, enabling them to be used for various bio-logical applications.5 However, the long chain lengths presentlimit the maximum achievable concentration of iron oxide in thedispersion. Harris et al.23 have achieved some of the highest ironoxide concentrations, up to 45.4wt% formagnetite nanoparticlescoated with triblock copolymers consisting of poly(ethyleneoxide) as end blocks and polyurethane as central block. We wereunable to prepare a ferrofluid that achieved spiking using theirmethod, even using dispersions at the highest possible concentra-tions. Those dispersions also formed a gel at concentrationsbeyond 40 wt % even after removing excess polymer by dialysis.We also noted that dispersions of triblock-coated nanoparticleswere unstable at pH>8 andmagnetic nanoparticles settled withina few hours, as the authors had stated.23

In another related study, Boyer et al.29 used hetrotelechelicpolymers of oligo(ethylene glycol acrylate), N-isopropylacryla-mide, and styrene for stabilizing nanoparticles. They found thatonly particles coated with poly(oligo(ethylene glycol acrylate))with high molecular weights (62 000 g/mol) were stable in phos-phate buffer solution, and then only for 48 h.Characterization of Magnetic Nanoparticles. The mag-

netic nanoparticles were characterized by several techniquesincludingTEM,FTIR,TGA, light scattering,XRD, andmagneto-metry.

Figure 3A shows the TEM images of sterically stabilizedmagnetic nanoparticles deposited on a carbon grid from aqueousdispersion. The particles are quite polydisperse, which is notunusual for particles prepared by this method and has been

reported previously.30 This micrograph is consistent with theaverage particle sizes determined by X-ray diffraction (6.2 nm)and from magnetometry (8.4 nm) discussed below. Electrostati-cally stabilized magnetic nanoparticles (Figure 3B) are more orless identical, except that these particles are a little bigger than thesterically stabilized ones. This can be attributed to batch to batchvariation in the synthetic procedures employed to prepare nano-particles

Figure 4 shows the FTIR spectrum of the pure polymer andthat of the sterically stabilizedmagnetic nanoparticles. The FTIRspectrum of the block copolymer is dominated by an intenseband at ∼1653 cm-1 attributed to the carbonyl stretching vibra-tion of the amide group of the acrylamide block.31 The shoulderat ∼1710 cm-1 is assigned to ν(CdO) of the carboxylic acidgroup.31 The bands at ∼1410-1450 cm-1 are assigned to C-Ostretching and OH deformation, respectively.31

Examination of the FTIR spectrum of the coated nanoparti-cles reveals that the shoulder in the spectrum of the pure poly-mer at 1710 cm-1, which originates from the ν(CdO) group of thecarboxylic acid, is no longer present and twopeaks at∼1400 cm-1

Figure 2. 65 wt % sterically stabilized aqueous ferrofluid in 2 MNaCl showing spiking in a magnetic field.

Figure 3. TEM images of (A) sterically and (B) electrostaticallystabilized nanoparticles.

(29) Boyer, C.; Bulmus, V.; Priyanto, P.; Teoh, W. Y.; Amal, R.; Davis, T. P.J. Mater. Chem. 2009, 19, 111.

(30) Sahoo, Y.; Goodarzi, A.; Swihart, M. T.; Ohulchanskyy, T. Y.; Kaur, N.;Furlani, E. P.; Prasad, P. N. J. Phys. Chem. B 2005, 109, 3879.

(31) Bellamy, L. J. The Infra-Red Spectra of Complex Molecules; Wiley:New York, 1975.

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and 1547 cm-1 have appeared. These bands correspond to thesymmetric and asymmetric vibrations of the COO- group, whichindicates bidentate bonding of the carbonyl groups to the surfaceFe atoms.32-35 This is due to binding of the carboxylic acidgroups from the acrylic acid block of the copolymer to the surfacehydroxyl groups of the nanoparticles to form carboxylate groupsas shown schematically in Figure 5 and previously proposed byother researchers.23,32-36

In addition, the position of the amide I band, observed at1653 cm-1 in the spectrum of the pure polymer, shifts to1658 cm-1 in the spectrum of the coated particles. This indicatesa change in the molecular environment of the amide group of thepolymer after its coating on the nanoparticle surface. The FTIRdata shown in Figure 4 thus support the model of chemicalbonding of the polymer to the particle as depicted in Figure 5.

TGA (Figure 6) shows a multistep weight loss profile for purecopolymer and a more gradual, almost single step weight lossprofile for nanoparticles coated with copolymer. While the netweight loss for the pure copolymer was 100% as expected, theweight loss for particles coated with polymer was only 24%,indicating 76% iron oxide in the polymer-coated nanoparticles.This exceeds the highest value previously achieved for anypolymer-coated dry magnetic iron oxide powder of 70 wt %.24

Calculated on the basis of a 7 nm diameter iron oxide core,24 wt% polymer corresponds to a polymer coating thickness ofabout 1 nm for the dried down particles.

The weight loss of the coated nanoparticles starts approxi-mately 80 �C higher than the pure copolymer (255 �C versus175 �C), due to the enthalpy of desorption of the copolymermolecules from the surface of the maghemite. Lin et al.36 haveinvestigated the stabilization of magnetite particles with poly-(acrylic acid) (PAA) and observed similar behavior. They sug-gested that initial weight losses in the temperature range 200-400 �C were due to dehydration and decarboxylation of thecarboxylic acid groups of the PAA oligomers while the maindegradation of polymer backbone occurred above 400 �C. In thepresent case, we also expect thermal degradation of the unat-tached poly(acrylamide) block. Thus, a smaller overall increase inthe degradation temperature range is expected in this systemcompared to pure PAA.36 However, it is to be noted that coatedparticles were dialyzed and dried before TGA, while the copoly-mer was simply dried without any further purification (i.e., notdialyzed). Thus, there may be some other impurities (such as salt,unreacted initiator, or some other byproducts) left along withcopolymer molecules, and this perhaps showed up in terms of thefinal weight loss step in the spectrogram of the neat polymerwhich is otherwise not seen in coated particles.

X-ray diffraction patterns of the dried magnetic nanoparticles(electrostatically and sterically stabilized) are shown in Figure 7.The XRD data from electrostatically stabilized nanoparticles isincluded for comparison. The XRD pattern of the materialreveals its crystalline nature, and the peaks match well with thosereported in literature for maghemite nanoparticles. The XRDspectrum of coated particles shows no dramatic change in itscrystalline structure (except a little broadening of the peaksat 2θ = 43.3� and 53.7�) as compared to the spectrum for theelectrostatically stabilized particles.

Nanocrystalite size can be estimated from the XRD data usingthe Debye-Scherrer equation,37

D ¼ 0:9λ

β cos θð1Þ

where D is the crystallite size (A), λ is the wavelength of X-rays(CuKR: λ=1.5418 A), θ is the diffraction angle, and β is the full

Figure 4. FTIR spectra of neat AA10-b-AAM14 block copolymerand AA10-b-AAM14-coated nanoparticles.

Figure 5. Poly(acrylic acid) block of the copolymer anchors ontothe nanoparticle surface via the carboxylic acid groups while thepoly(acrylamide) block extends into water and provides stericstabilization.

Figure 6. Thermogravimetric analysis of sterically stabilizednanoparticles (solid line) and neat copolymer (O).

(32) Rocchiccioli-Deltche, C.; Franck, R.; Cabuil, V.;Massart, R. J. Chem. Res.1987, 5, 126.(33) Moore, R. G. C.; Evans, S. D.; Shen, T.; Hodson, C. E. C. Phys. E 2001, 9,

253.(34) Shukla, N.; Liu, C.; Jones, P. M.; Weller, D. J. Magn. Magn. Mater. 2003,

266, 178.(35) Liu, Q.; Xu, Z. Langmuir 1995, 11, 4617.(36) Lin, C.-L.; Lee, C.-F.; Chiu, W.-Y. J. Colloid Interface Sci. 2005, 291, 411. (37) Cullity, B. D. Elements of X-ray Diffraction; A.W. P. C., Inc.: MA, 1967.

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width at half-maximum (in radians). The crystallite sizes (7 nm forthe electrostatically stabilized particles and 6.2 nm for thesterically stabilized particles) obtained from the above equationare in good agreement with those obtained from TEM measure-ments suggesting that the particles are monocrystalline.

Figure 8 shows the magnetization curves of dried powders ofboth the electrostatically and sterically stabilized nanoparticlesdetermined by vibrating sample magnetometry at room tempera-ture. The variation of magnetization, M, in each case, withapplied field,H, shows no hysteresis; that is, both the remanenceand coercivity are zero. The data are well described by theLangevin equation,28 indicating that the magnetic nanoparticlesare single domain and the samples have superparamagneticbehavior at room temperature, as expected for the nanoscaledimension of the particles. The absence of hysteresis was alsoconfirmed by measuring the magnetization for both of thesamples at relatively weaker field strengths (i.e., between(0.002 T).

Since the magnetization of the sample follows the Langevinfunction, this can be used to derive the magnetic domain size.38,39

According to Chantrell et al.,40 who assume a log-normal sizedistribution,41 both the magnetic particle diameter, Dm, and thestandard deviation, σ, can be derived from

Dm ¼ 18kBT

πms

ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiχi

3Ms

1

H0

s24

351=3

;

σ ¼ 1=3 ln3χiMs

=1

H0

� �" #1=2

ð2Þ

where Ms and ms are the saturation magnetization of thenanoparticles and the bulk phase, respectively, χi is the initialsusceptibility calculated at low field, in the region where thevariation of M against H is linear, and 1/H0 is obtained byextrapolating M to 0 at high fields, in the region where therelationship between M and 1/H is a straight line.

By this approach, domain diameters of 8.37 nm (σ=0.01) and6.7 nm (σ = 0.3) were obtained for the electrostatically and thesterically stabilized particles, respectively, and are consistent withthe particle sizes obtained by other techniques. This batch ofsterically stabilized particles is uniformly found to be smaller thanthe reference system of electrostatically stabilized particles. Theseresults are also consistent with the work of Morales et al.42 whodemonstrated that nanoparticle sizes obtained from magnetiza-tion data agreed well with those obtained by TEM for smallerparticles (i.e., 3-5 nm) whereas in larger particles (i.e., 8-12 nm)sizes obtained from magnetization measurements were smallerthan those from TEM. Harris et al.23 similarly found goodagreement in particle sizes derived from different techniques fortheir triblock copolymer-coated magnetite particles.

The saturation magnetization (Ms = 2.81 � 105 A/m) of theelectrostatically stabilized nanoparticles is lower than that of puremaghemite (Ms=3.67 � 105 A/m).43 This has been attributedelsewhere to the presence of nonmagnetic or “dead” surface layersresulting from the chemical reaction between the stabilizingsurfactant and the ferrite particles.38 Such dead surface layersmake the magnetic diameter of the particles smaller than itsphysical diameter. Nanoparticles coated with copolymer showeda still lower value of saturation magnetization (Ms = 1.95 � 105

A/m). Davies et al.44 have suggested that particles containingsufficient concentrations of functional groups allowed for spin-pinning of the iron oxide surfaces, which gives rise to a noncol-linear spin structure and is known to produce reduced magneticmoments for the particles.44-46

Size Distribution of Nanoparticle Dispersions. Using asimilar preparative method, somewhat larger magnetic particleswere prepared and stabilized using a AA10-b-AAM19 diblockcopolymer. The size distribution of coated and uncoated nano-particles was determined in 0.1 wt%dispersions by dynamic lightscattering as shown in Figure 9. This reveals that the distributionof hydrodynamic diameters of the magnetic nanoparticles beforecoating with polymer is between 10 and 60 nm, with a z-average

Figure 7. X-ray diffraction patterns of dry powders of electrosta-tically (solid line) and sterically stabilized nanoparticles (dottedline).

Figure 8. Magnetization versus applied field curves of electrosta-tically stabilized (O) and sterically stabilized nanoparticles (4).Solid lines are the fits of the experimental data to the Langevinfunction.28

(38) Chantrell, R. W.; Popplewell, J.; Charles, S. W. IEEE Trans. Magn. 1978,Mag-14, 975.(39) Feltin, N.; Pileni, M. P. Langmuir 1997, 13, 3927.(40) Chantrell, R. W.; Popplewell, J.; Charles, S. W. Physica 1977, 86-88B,

1421.(41) O’Grady, K.; Bradbury, A. J. Magn. Magn. Mater. 1983, 39, 91.

(42) Morales, M. P.; Veintemillas-Verdaguer, S.; Montero, M. I.; Serna, C. J.Chem. Mater. 1999, 11, 3058.

(43) Saravanan, P.; Alam, S.; Mathur, G. N. J. Mater. Sci. Lett. 2003, 22, 1283.(44) Davies, K. J.; Wells, S.; Charles, S. W. J. Magn. Magn. Mater. 1993, 122,

24–28.(45) Coey, J. M. D. Phys. Rev. Lett. 1971, 27, 1140–1142.(46) Morup, S. J. Magn. Magn. Mater. 1983, 39, 45–47.

DOI: 10.1021/la903513v 4471Langmuir 2010, 26(6), 4465–4472

Jain et al. Article

diameter of 21.3 nm. The dilution of the nanoparticle dispersionto 0.01 wt% gave the same average diameter. The hydrodynamicdiameter of the nanoparticles increased by about 9 nm after poly-mer adsorption yielding an average of 30.3 nm. This is in a verygood agreement with the expected layer thickness of about 4.5 nmdue to the solvation and extension of the poly(acrylamide) stabiliz-ing blocks. In our earlier work on the stabilization of latex particlesby short hydrophilic blocks, we found that the hydrated stabilizingcorona of poly(acrylic acid) stabilized latex particles extended intothe aqueous phase a distance equivalent to approximately theaverage stretched out length of the hydrophilic AA block.47

Stability of Nanoparticle Dispersions. The stability ofthe sterically stabilized nanoparticles was investigated in 0.1wt % dispersions by dynamic light scattering at different electro-lyte concentrations and pH, as shown in Figure 10. The z-averageparticle diameter changes little as the concentration of ammo-nium nitrate is increased from 0 up to a saturated solution,that is, 60 wt % (Figure 10A). This demonstrates the highlyeffective steric stabilization of these particles even at extreme ionicstrengths. Such behavior has not been previously reported.23,36,48

Figure 10B shows the time-dependence of the average particlediameter when dispersed in a 10 wt % solution of ammoniumnitrate. The nanoparticles showed no increase in their sizeover 16 h.

Figure 10C shows the effect of pH on the stability of a series ofnanoparticle dispersions, all taken from a single batch. Theparticles are stable over the very wide pH range of 4-12, andimportantly near neutral pH and near the isoelectric point ofγ-Fe2O3 (pH ∼ 6.8). Measurements taken 30 min and 24 h afteradjusting the pH of the nanoparticle dispersions show no notice-able differences in the sizes of the particles in the pH range 4-12.The slight decrease in size with increasing pH may be due tofurther deprotonation of carboxylic acid groups of the PAAblockof the copolymer, facilitating stronger adsorption on the nano-particle surface. Particle dispersions were unstable above pH 12and below 3.5. Below pH 3.5, the dispersion rapidly destabilizes.Here the acrylic acid block of the polymer will be substantiallyprotonated, which causes the copolymer to desorb from the

surface of the nanoparticles, destabilizing the dispersion.Dispersions at pHs higher than 12 were also unstable andflocculated very rapidly. It appears here that the copolymer is

Figure 9. Hydrodynamic (z-average) diameters of dilute disper-sions of coated and uncoated nanoparticles.

Figure 10. Hydrodynamic (z-average) diameters of dilute disper-sions of sterically stabilized nanoparticles (A) as a function ofammonium nitrate concentration; (B) in 10 wt % ammoniumnitrate solution; and (C) as a function of dispersion pH after (O)30 min and (4) 24 h.

(47) Ganeva, D. E.; Sprong, E.; de Bruyn, H.; Warr, G. G.; Such, C. H.;Hawkett, B. S. Macromolecules 2007, 40, 6181–89.(48) Wang, Y.; Wong, J. F.; Teng, X.; Lin, X. Z.; Yang, H. Nano Lett. 2003, 3,

1555.

4472 DOI: 10.1021/la903513v Langmuir 2010, 26(6), 4465–4472

Article Jain et al.

fully deprotonated and the particle surface is highly negativelycharged, even at high electrolyte concentrations. Under thesecircumstances, the copolymerwill desorb from the particle surfacedue to electrostatic repulsions, leading to particle flocculation.

Conclusions

We have described the development of a simple, versatile,magnetic, aqueous nanoparticle dispersion stabilized by an ultra-thin, strongly surface-bound, polymeric, steric stabilization layer.These coated particles suffer no measurable polymer desorptionat high dilutions, but they can also be concentrated sufficiently toform a spiking ferrofluid (>1017 particles/mL) that remainsstable under challenging solution conditions for at least severalmonths.

The long-term stability of these dispersions in concentratedform as well as at high dilution, in high ionic strength, and overa broad pH range suggests that they should be suitable candi-dates for a variety of biomedical applications including asMRI contrast agents and for hyperthermia treatments. Thesimplicity and versatility of the RAFT process for designingthe copolymer block architecture also enables easy incorporation

of a wide variety of functional groups for tailored biocompati-bility and biorecognition purposes, and ready attachment oforganic moieties such as cancer-targeting ligands, proteins, drugs,and so on. These features will facilitate the development of thesecoated nanoparticles as targeted imaging and therapeutic deliveryagents.

Numerous other uses can also be envisaged for these aqueousferrofluids or dilute magnetic dispersions where high salinity orsalt sensitivity may otherwise compromise performance or long-evity, including oil-field applications, liquid seals, motion sensors,and braking fluids.

Acknowledgment. The authors thank Dr. Stephen Collocottof CSIRO Materials Science and Engineering for carrying outsaturation magnetization experiments, E. H. Pan for assistancewith some of the light scattering experiments, and Dr. ElizabethCarter of the Sydney University Vibrational Spectroscopy Faci-lity for help in interpreting FTIR spectra. This work was sup-ported by Australian Research Council Linkage Project grants inpartnership with Dyno Nobel Asia Pacific Limited and SirtexMedical Limited.