Au Shell Nanoparticles by Iterative

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Synthesis of Fe Oxide Core/Au Shell Nanoparticles by Iterative Hydroxylamine Seeding

2004 Vol. 4, No. 4 719-723

Jennifer L. Lyon,† David A. Fleming,† Matthew B. Stone,‡ Peter Schiffer,‡ and Mary Elizabeth Williams* Department of Chemistry, The PennsylVania State UniVersity, 152 DaVey Laboratory, UniVersity Park, PennsylVania 16802, and Department of Physics and Materials Research Institute, The PennsylVania State UniVersity, 104 DaVey Laboratory, UniVersity Park, PennsylVania 16802 Received December 30, 2003; Revised Manuscript Received February 26, 2004

ABSTRACT Water-soluble, Au-coated magnetic Fe oxide nanoparticles with diameters ∼60 nm were synthesized by the reduction of Au3+ onto the surfaces of ∼9 nm diameter particles consisting of either γ-Fe2O3 or partially oxidized Fe3O4 via iterative hydroxylamine seeding. The morphology and optical properties of the core/shell particles are dependent on the quantity of deposited Au, while the magnetic properties remain largely independent of Au addition. The Au-coated particles exhibit a surface plasmon resonance peak that blue-shifts from 570 to 525 nm with increasing Au deposition. SQUID magnetometry reveals that particle magnetic properties are not affected by the overlayer of a moderately thick Au shell.

Iron oxide nanoparticles consisting of maghemite (γ-Fe2O3) or magnetite (Fe3O4) have attracted much interest due to their widespread electronic and, more recently, biomedical applications. In particular, solutions of γ-Fe2O3 and Fe3O4 particles 7.5-100 nm in diameter have shown promise as magnetic fluids for targeted drug delivery.1 Superparamagnetic Fe oxide particles (3-10 nm) coated with glucose polymers have been manipulated by external magnetic forces to promote site-specific inactivation of cancerous cells.2 They have also been implemented in magnetic cell sorting and immunoassays.1 The extent of biomedical applicability of these particles depends strongly upon their stability in solutions of physiological pH, as well as the degree to which their surfaces may be chemically functionalized. Fe oxide applicability is notably hindered by the materials’ spontaneously oxidizable surfaces; chemical methods to predictably tune surface functionality are still being explored. However, it is well established that Au nanoparticle surfaces may be repeatedly functionalized with thiolated organic molecules.3 Placement of a functional group on the terminal end of the alkanethiolate imparts further chemical reactivity and the opportunity to create multifunctional, reactive nanoparticles. For example, Murray et al. have covalently linked coenzyme A to the * Corresponding author. Phone: (814) 865-8859, fax: (814) 863-8403, email: [email protected]. † Department of Chemistry. ‡ Department of Physics and Materials Research Institute. 10.1021/nl035253f CCC: $27.50 Published on Web 03/20/2004

© 2004 American Chemical Society

surfaces of Au particles via amide coupling chemistry.3b Mirkin et al. have successfully coordinated thiol-modified DNA molecules to Au particles; this particle system has been further manipulated using various enzymes.4 We reasoned that the ability to tune chemical functionality based on alkanethiolate adsorption onto Au surfaces, when combined with magnetically susceptible Fe oxide particles, will provide a novel avenue toward using magnetic nanoparticles for targeted drug delivery. Although monometallic Fe oxide particles have been extensively investigated, there are few examples describing the synthesis and physical properties of core/shell nanoparticles containing γ-Fe2O3 or Fe3O4. To maximize the tunability of chemical functionality and, ultimately, biological applicability, a thorough understanding of the magnetic, electronic, and optical properties of core/shell systems as a function of composition is essential. While similar magnetic core/shell particles have been synthesized in microemulsions,5 we utilize an aqueous-based synthesis, which creates particles that are stable at physiological pHs. This paper describes the preparation of two series of water-soluble core/ shell nanoparticles utilizing both γ-Fe2O3 and oxidized Fe3O4 cores with Au shells, and compares the optical and magnetic properties of the two systems. The morphology of prepared Fe oxide particles depends largely upon the route chosen for its synthesis.6 Initially, Fe3O4 particles are prepared by coprecipitation of an Fe(II)

and Fe(III) salt in alkaline medium. A magnetite-like, defected inverse spinel structure (γ-Fe2O3) can then be obtained by gently heating an aqueous solution of Fe3O4 in air. The oxidation of Fe3O4 to γ-Fe2O3 in aqueous solutions exposed to air at room temperature also occurs, albeit much more slowly. Once oxidized to γ-Fe2O3, the magnetic fluid is remarkably stable, lasting for years in acidic or alkaline medium.7 Stability is maintained by electrostatic and repulsive interactions between counterions in solution and amphoteric hydroxyl ions adsorbed onto particle surfaces during synthesis. The nature of these adsorbed ions (H3O+ or OH-) is determined by solution pH.8 The Fe3O4 nanoparticles (cores) were prepared by coprecipitation of Fe(II) and Fe(III) chlorides (FeII/FeIII ratio ) 0.5) with 1.5 M NaOH as the reductant.9 The black precipitate was collected on a magnet, washed twice with H2O, twice with 0.1 M tetramethylammonium hydroxide (TMAOH), and isolated via centrifugation before being taken up finally in 0.1 M TMAOH.10 To synthesize γ-Fe2O3 nanoparticles, freshly nucleated Fe3O4 particles were washed with 0.1 M HNO3 and isolated by centrifugation. The particles were dissolved in 0.01 M HNO3 and heated with stirring at 90-100 °C for 30 min to completely oxidize the particles to γ-Fe2O3.7 The solution was cooled to room temperature, centrifuged, and the supernatant decanted. The isolated particles were washed twice with H2O and suspended in 0.1 M TMAOH. In both the Fe3O4 and γ-Fe2O3 nanoparticle syntheses, the final concentration of particles was ∼36 mM and pH ) 12 when suspended in TMAOH. At this pH, interactions between N(CH3)4+ counterions and adsorbed OH- anions stabilize the solution and prevent particle aggregation.8 Particle solutions were stored on the benchtop and remained stable for several months. Au shells were formed by reduction of Au3+ onto the Fe oxide surfaces using a modification of Brown and Natan’s iterative hydroxylamine seeding procedure.11 In control experiments, no reaction was observed for solutions containing only Fe oxide particles and hydroxylamine. Furthermore, no reduction of the HAuCl4 occurred in Fe oxide solutions without added hydroxylamine. These observations are consistent with the hydroxylamine promoting Au3+ surfacecatalyzed reduction, rather than monometallic Au particle nucleation or a galvanostatic reaction.12 The Fe oxide solutions were each diluted to 1.1 mM in water and stirred with an equal volume of 0.1 M sodium citrate for 10 min to exchange adsorbed OH- with citrate anions. The Fe oxide/citrate solution was diluted 20-fold with H2O (to 5 mM citrate), and aliquots of 1% HAuCl4 were incrementally added (with at least 10 minutes between additions) along with an excess of 0.2 M NH2OH‚HCl (see Supporting Information). A total of five additions were performed; the clear solution became purple upon addition of Au3+ and gradually changed to deep pink during the successive iterations. Particle stability upon addition of an Au shell is largely controlled by the stabilizing ligands’ point of zero charge (PZC); when the PZC is reached, counterion charges are too 720

weak to repel particles and aggregation occurs.8b Because Au3+ was added in acidic form, the pH of the solution dropped roughly 1 pH unit per iteration. Nanoparticle aggregation was observed in solutions with pH of ∼6, where the counterions stabilizing the core/shell particles appear to be a mixture of both OH- (PZC ) 8) and citrate (PZC ) 2) anions.8b The solution retained a faint purple or pink color even after particles had aggregated, suggesting that a small fraction of citrate-stabilized Fe/Au particles remained stable in solution. Initial attempts to overlay Au shells onto freshly synthesized Fe3O4 particle surfaces failed to yield any evidence of Au reduction. Specifically, it was observed that freshly prepared Fe3O4 nanoparticles (i.e, within 24 h of nucleation) failed to obtain an Au shell. Generally, a maximum of two iterations could be performed before the Fe3O4 particles aggregated and precipitated from solution. However, using Fe3O4 nanoparticle solutions that were exposed to air for extended periods (g 1 week), sequential addition of AuCl4led to the formation of stable and soluble core/shell nanoparticles. It is well known that long-term exposure of Fe3O4 to air results in particle oxidation to form γ-Fe2O3 via Fe cation diffusion;6b,c these observations suggest that Au3+ preferentially reduces onto γ-Fe2O3 surfaces rather than Fe3O4. The cause for this difference in deposition behavior is unclear; since the lattice parameters of Fe3O4 and γ-Fe2O3 are nearly identical (a ) 0.840 and 0.835 nm, respectively; see below),6a a lattice mismatch is not a likely explanation. To confirm the observed behavior of oxidized Fe3O4, γ-Fe2O3 nanoparticles were synthesized and Au3+ iteratively reduced on their surfaces using the above method. The remainder of this report compares the properties of the two series of Aucoated Fe oxide nanoparticles, Au-coated γ-Fe2O3 vs partially oxidized Fe3O4. These particles were characterized by transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), UV-visible absorption spectroscopy, and SQUID magnetometry. The sizes and compositions of the Au-coated Fe oxide nanoparticles were analyzed for each iteration of Au deposited using TEM and EDS. Representative TEM images of the as-prepared γ-Fe2O3 particles and particles resulting from the first, third, and fifth iterative additions of Au3+ are shown in Figure 1. Particle diameters were determined by measuring the long axis of each particle, and histograms recording particle diameter are shown in each inset. The average diameter of the Fe2O3 nanoparticles (Figure 1A) is 9 ( 3 nm; iterative addition of Au3+ and hydroxylamine initially increases the average diameter and affects the surface morphology. We have observed that partially oxidized Fe3O4 nanoparticles are more resistant to Au deposition than are γ-Fe2O3 particles; in TEM images of early iterations with Fe3O4, bare core particles are often visible, suggesting that Au3+ reduction may preferentially occur at more oxidized sites. The TEM images further show that the surfaces of the core/shell particles are jagged after the initial addition of Au3+ and hydroxylamine to the γ-Fe2O3 solution, but become more spherical following subsequent iterations. Particle Nano Lett., Vol. 4, No. 4, 2004

Figure 2. EDS spectrum of the same sample used to obtain Figure 1C, with identification of the observed peaks. Cu peaks appear due to scattering caused by the Cu TEM grid.

Figure 1. Representative TEM images of citrate-stabilized γ-Fe2O3/ Au core/shell nanoparticles with (A) zero (i.e., pure γ-Fe2O3), (B) one, (C) three, and (D) five incremental additions of Au3+ to the γ-Fe2O3/H2O solution. Insets: Histograms of the particle diameters for (A) 533 particles; (B) 161 particles; (C) 267 particles; (D) 294 particles.

analysis reveals that the average particle diameters remain roughly constant throughout all iterations, but the particles become more uniform in size (i.e., less polydisperse). The measured average diameters and polydispersities for Figures 1B, C, and D are 62 ( 19 nm (31% polydispersity), 59 ( 19 nm (32% polydispersity), and 57 ( 14 nm (25% polydispersity), respectively. Results from TEM imaging of partially oxidized Fe3O4/Au core/shell particles (Supporting Information) exhibit similar morphological changes. In both cases, the images suggest that Au3+ initially reduces onto specific sites of the Fe oxide core surface, resulting in the jagged appearance. Further reductions apparently fill these empty surface sites with Au, producing more spherical particles. This is likely driven by the lower energy required for Au atoms to adsorb onto sites most similar in structure to bulk Au (i.e., with many Au atomic neighbors). To confirm the composition of the particles, EDS spectra were collected during TEM imaging. A representative EDS spectrum, taken from the sample shown in Figure 1C, is shown in Figure 2. This spectrum confirms the presence of both Fe and Au in the particles (though it does not confirm a core/shell structure). The relative intensities of the Au and Fe peaks indicate that the particles are largely of Au character, correlating with the calculated molar ratios of Au3+ to Fe oxide (see Supporting Information). In pure Au nanoparticles, the collective oscillations of free electrons, known as the surface plasmon (SP), cause an absorption peak to appear in the visible region of the electromagnetic spectrum.13 Factors that affect the position Nano Lett., Vol. 4, No. 4, 2004

Figure 3. UV-vis spectra of as synthesized γ-Fe2O3/Au nanoparticles. Spectra for pure γ-Fe2O3 particles as well as spectra for Au iterative addition numbers 1-5 are presented.

of the SP peak have been investigated on the basis of Mie theory; for Au nanoparticles, the SP has been shown to shift as a function of particle size, stabilizing ligand and solvent dielectric.14,15 In particular, citrate-stabilized Au particles in water have been shown to exhibit a SP peak at 520 nm.11 Thus, the bimetallic core/shell nanoparticles were further characterized by UV-visible absorption spectroscopy to compare their optical properties to those of monometallic Au particles. Spectra of as-prepared core/shell nanoparticles for each iterative Au deposition were collected and are shown in Figure 3. As the ratio of Au to Fe oxide increases, the SP peak blue-shifts toward the value expected for pure citratestabilized Au particles, as plotted in Figure 4. The observed increase in energy may have multiple causes. For example, Templeton et al. have found that quantitatively altering pure Au cores via electronic charging caused a SP shift.15c Thus, the electronic properties induced by the presence of a different (Fe oxide) core may also affect SP position; as Au character increases and the Fe oxide becomes buried beneath the Au shell, these dielectric effects may be suppressed. The lack of a uniform Au shell around the cores may also affect SP peak position. Later iterations, in which the Au 721

Figure 4. Plot of average SP peak (from three separate trials) as a function of Au mole fraction for citrate-stabilized γ-Fe2O3/Au (b) and partially oxidized Fe3O4/Au (() core/shell nanoparticles in water compared to the standard SP peak of citrate-stabilized pure Au particles (open diamond). Lines are used to guide the eye.

Figure 6. Magnetization measurements as a function of applied field for pure γ-Fe2O3 nanoparticles (A) and for γ-Fe2O3/Au core/ shell nanoparticles (B). Measurements were taken at 5 K. Plots are normalized to the mass of γ-Fe2O3.

Figure 5. Measured magnetization moments as a function of temperature after cooling in zero field (2) and in a 100 Oe field (9) for pure γ-Fe2O3 nanoparticles (A) and for γ-Fe2O3/Au core/ shell nanoparticles (B). Plots are normalized to the mass of γ-Fe2O3.

shell has filled in more completely, exhibit SP peaks nearer to that of pure Au particles. Jensen et al. have previously noted that changing particle morphology to a more spherical shape results in a blue-shift.15a Ongoing experiments aim to investigate these and similar magnetic core/shell particle systems to determine the structural effects on SP energies. SQUID magnetometry reveals that overlaying Fe oxide particle surfaces with a shell of Au has a negligible effect 722

on magnetic behavior. Figure 5 shows the field cooled and zero field cooled behavior of both pure γ-Fe2O3 (A) and synthesized γ-Fe2O3/Au core/shell particles. It can be seen that upon Au coating, the blocking temperature decreases with a corresponding increase in the magnetic moment. This is attributed to the aggregated nature of the pure γ-Fe2O3 nanoparticles, which produces a state reminiscent of the bulk material. The Au shell allows each γ-Fe2O3 particle to behave independently, and interparticle interactions are therefore not important. The blocking temperature of the Au coated γ-Fe2O3 particles is similar to those reported in the literature for uncoated nanoparticles. In both the pure and the Au coated particles, a slight magnetic hysteresis is observed below the blocking temperature. This is seen in Figure 6, which depicts particle magnetic response to a varying magnetic field. The hysteresis in both samples is observed to be 37 Oe at 5 K while the saturation magnetization for both γ-Fe2O3 (41 emu/g) and γ-Fe2O3/Au nanoparticles (45 emu/g) are the same within experimental error. In conclusion, this synthesis provides a rapid and effective route to magnetic core/shell particles that are soluble in aqueous media. We have demonstrated that either γ-Fe2O3 or partially oxidized Fe3O4 may be used as cores. The asprepared particles are relatively uniform in size, but continuing efforts should improve monodispersity and separate the core/shell particles from any nonmagnetic (i.e., pure Au) particles. Nano Lett., Vol. 4, No. 4, 2004

Acknowledgment. This work was supported by a CAREER grant from the National Science Foundation, (to M.E.W. CHE-0239-702) and by the American Chemical Society Petroleum Research Fund (to M.E.W., 37553-G4) and the Pennsylvania State University Undergraduate Research Office. P.S. acknowledges support under NSF DMR grant #0101318. We thank Professor Tom Mallouk for use of the XRD. Supporting Information Available: Detailed synthetic procedure and crystallographic, TEM, and UV-vis data for both series of particles. This material is available free of charge via the Internet at http://pubs.acs.org. References (1) (a) Halbreich, A.; Roger, J.; Pons, J. N.; Geldwerth, D.; Da Silva, M. F.; Roudier, M.; Bacri, J. C. Biochim. 1998, 80, 379-390. (b) Scientific and Clinical Applications of Magnetic Carriers; Hafeli, U., Schutt, W., Teller, J., Zborowski, M., Eds; Plenum Press: New York, 1997. (2) Jordan, A.; Scholz, R.; Peter, W.; Fahling, H.; Felix, R. J. Magn. Magn. Mater. 1999, 201, 413-419. (3) (a) Brust, M.; Walker, M.; Bethell, D.; Schiffrin, D.; Whyman, R. J. Chem. Soc. Chem. Commun. 1994, 801-802. (b) Templeton, A.; Chen, S.; Gross, S.; Murray, R. W. Langmuir 1999, 15, 66-76. (4) (a) Storhoff, J. J.; Elghanian, R.; Mucic, R. C.; Mirkin, C. A.; Letsinger, R. L. J. Am. Chem. Soc. 1998, 120, 1959-1964. (b) Kanaras, A. G.; Wang, Z.; Bates, A. D.; Cosstick, R.; Brust, M. Angew. Chem., Int. Ed. 2003, 42(2), 191-194.

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(5) Lin, J.; Zhou, W.; Kumbhar, A.; Wiemann, J.; Fang, J.; Carpenter, E. E.; O’Connor, C. J. J. Solid State Chem. 2001, 159, 26. (6) (a) Cornell, R. M.; Schwertmann, U. The Iron Oxides; VCH: New York, 1996. (b) Jolivet, J. P.; Tronc, E. J. Colloid Interface Sci. 1988, 125, 688-701. (c) Swaddle, T. W., Oltmann, P. Can. J. Chem. 1980, 58, 8(17), 1763-1772. (7) Lefebure, S.; Dubois, E.; Cabuil, V.; Neveu, S.; Massart, R. J. Mater. Res. 1998, 13(10), 2975. (8) (a) Massart, R. IEEE Trans. Magn. 1981 17(2), 1247-48. (b) Bacri, J.; Perzynski, R.; Salin, D. J. Magn. Magn. Mater. 1990 85, 27-32. (9) Kang, Y. S.; Risbud, S.; Rabolt, J. F.; Stroeve, P. Chem. Mater. 1996, 8, 2209-2211. (10) Philipse, A. P.; van Bruggen, M. P. B.; Pathmamanoharan, C. Langmuir 1994, 10, 92-99. (11) Brown, K. J.; Walter, D. G.; Natan, M. J. Chem. Mater 2000, 12, 306-313. (12) Stremsdoerfer, G.; Perrot, H.; Martin, J. R.; Clechet, P. J. Electrochem. Soc. 1988, 135(11), 2881-2885. (13) Creighton, J. A.; Eadon, D. G.; J. Chem. Soc., Faraday Trans. 1991, 87(24), 3881-3891. (14) (a) Jensen, T. R.; Malinsky, M. D.; Haynes, C. L.; Van Duyne, R. P. J. Phys. Chem. B 2000, 104, 10549-10556. (b) Mulvaney, P. Langmuir 1996, 12, 788-800. (c) Xu, M.; Dignam, M. J. J. Chem. Phys. 1992, 96(5), 3370-3378. (15) (a) Jensen, T. R.; Duval, M. L.; Kelly, K. L.; Lazarides, A. A.; Schatz, G. C.; Van Duyne, R. P. J. Phys. Chem. B 1999, 103, 9846-9853. (b) Underwood, S.; Mulvaney, P.; Langmuir 1994, 10, 3427-3430. (c) Templeton, A. C.; Pietron, J. J.; Murray, R. W.; Mulvaney, P. J. Phys. Chem. B 2000, 104, 564-570.

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