Surfactant-Free Preparation and Drug Release Property of Magnetic

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J. Phys. Chem. C 2008, 112, 12149–12156

12149

Surfactant-Free Preparation and Drug Release Property of Magnetic Hollow Core/Shell Hierarchical Nanostructures Shao-Wen Cao and Ying-Jie Zhu* State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, P. R. China, and Graduate School of Chinese Academy of Sciences, Shanghai, P. R. China ReceiVed: April 11, 2008; ReVised Manuscript ReceiVed: June 4, 2008

We report the preparation of a novel kind of nanoporous hollow core/shell hierarchical nanostructures of iron oxide (γ-Fe2O3 or Fe3O4) with a high specific surface area, whose morphological feature is characterized as hierarchically nanostructured complex architectures self-assembled by nanosheets of the same kind of iron oxide with the spherical core inside the hollow sphere and circular empty space in between the core and hollow sphere. The precursor with the similar hollow core/shell hierarchical morphology is synthesized using FeCl3 and urea in ethylene glycol in the absence of any surfactant by a solvothermal method at 160 °C for 15 h. The precursor is used to prepare γ-Fe2O3 and Fe3O4 with well-preserved morphological architectures by a thermal transformation strategy. The formation mechanism of the precursor and the effects of the reactant concentration and reaction temperature are discussed. The BET surface areas and the magnetic properties of as-prepared iron oxides are investigated. The drug storage and in vitro release property of the PEG-modified Fe3O4 sample are studied. The PEG-modified Fe3O4 sample has a high drug loading capacity and favorable drug release property. Introduction Inorganic core-shell nanostructures have attracted much attention due to their unique structure and interesting properties, thus having wide potential applications in biotechnological, optical, electronic, magnetic, catalytic and sensing devices.1–9 However, most core/shell nanostructures reported consist of two different kinds of materials,10 one material for the core and another for the shell, here we call these core/shell nanostructures “heterogeneous core/shell nanostructures”. In contrast, “homogeneous core/shell nanostructures” are totally different, which consist of only one kind of material (the same material for both the core and the shell). Compared with heterogeneous core/ shell nanostructures, the homogeneous core/shell nanostructures are much more difficult to prepare, and only a few examples have been reported.11–15 Recently, Liu and Zeng16 reported the preparation of homogeneous core/shell structures of ZnS via the Ostwald ripening. It is a great challenge to develop simple and novel synthetic methods for homogeneous core/shell nanostructures with designed chemical composition and controlled morphologies. Moreover, the hierarchical nanostructures are also promising candidates for new functional materials. So far, a variety of hierarchical structures, for example, cubic PbS17 and noble metals,18 hexagonal Fe2O319 and HgS,20 tetragonal tungstate,21 PbMoO4,22 orthorhombic Bi2S3,23 Ni(OH)2 and NiO,24 and Co(OH)2 and Co3O4,25 have been reported. γ-Fe2O3 and Fe3O4 are very important functional materials due to their advantages such as magnetic properties, chemical stability, biocompatibility, and low toxicity. They are widely used in magnetic storage media,26 clinical diagnosis and treatment,27,28 and so on. Various nanostructures of γ-Fe2O3 and Fe3O4, such as nanocrystals,29,30 nanowires,31 nanoneedles,32 * Corresponding author. Telephone: +86-21-52412616. Fax: +86-2152413122. E-mail: [email protected].

nanorods,33 nanoplates,34 nanotubes,35,36 hollow spheres,37 and architectures,38 have been successfully fabricated by a variety of methods. Herein, we report for the first time the preparation of a novel kind of hollow core/shell hierarchical nanostructures with a high specific surface area, which combine the advantages of core/ shell nanostructures with the same chemical composition and circular empty space in between the core and the shell, hierarchical and nanoporous structure and self-assembly, that is to say, novel hierarchically nanostructured complex architectures self-assembled by nanosheets of the same kind of iron oxide (γ-Fe2O3 or Fe3O4) with the spherical core in the hollow sphere and circular empty space in between the core and hollow sphere. To the best of our knowledge, there has been no report on the preparation and properties of such hollow core/shell hierarchical nanostructures of iron oxides (γ-Fe2O3 and Fe3O4). Experimental Section Characterization of Samples. The prepared samples were characterized using X-ray powder diffraction (XRD) (Rigaku D/max 2550 V, Cu Ka radiation, λ ) 1.54178 Å), scanning electron microscopy (SEM) (JEOL JSM-6700F), and transmission electron microscopy (TEM) (JEOL JEM-2100F). The thermogravimetric analysis (TG) and differential scanning calorimetric (DSC) curves were taken on a STA 409/PC simultaneous thermal analyzer (NETZSCH, Germany) with a heating rate of 10 °C in a flowing air. The Brunauer-EmmettTeller (BET) surface area and pore size distribution were measured with an accelerated surface area and porosimetry system (ASAP 2010). A physical property measurement system (PPMS) was used to evaluate the magnetic properties at room temperature. The ibuprofen concentrations were analyzed using a UV-vis spectrophotometer (UV-2300, Techcomp) at a wavelength of 263 nm.

10.1021/jp803131u CCC: $40.75  2008 American Chemical Society Published on Web 07/16/2008

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TABLE 1: Experimental Conditions for the Preparation of Some Typical Samplesa sample no. 1 2 3 4 5 6 7 8 9 a

reaction system 0.135 0.135 0.135 0.135 0.135 0.135 0.101 0.068 0.135

g g g g g g g g g

of of of of of of of of of

FeCl3 · 6H2O FeCl3 · 6H2O FeCl3 · 6H2O FeCl3 · 6H2O FeCl3 · 6H2O FeCl3 · 6H2O FeCl3 · 6H2O FeCl3 · 6H2O FeCl3 · 6H2O

+ + + + + + + + +

0.08 0.08 0.08 0.08 0.08 0.08 0.06 0.04 0.08

g g g g g g g g g

of of of of of of of of of

solvothermal temperature and time

morphology

160 °C and 15 h 160 °C and 2 h 160 °C and 3 h 160 °C and 6 h 160 °C and 9 h 160 °C and 12 h 160 °C and 15 h 160 °C and 15 h 200 °C and 15 h

hollow core/shell hierarchical nanostructures nanosheets hierarchically nanostructured spheres compact hierarchically nanostructured spheres core/shell hierarchical nanostructures hollow core/shell hierarchical nanostructures hollow core/shell hierarchical nanostructures hollow core/shell hierarchical nanostructures dispersed nanosheets

CO(NH2)2 CO(NH2)2 CO(NH2)2 CO(NH2)2 CO(NH2)2 CO(NH2)2 CO(NH2)2 CO(NH2)2 CO(NH2)2

In all experiments, 25 mL of ethylene glycol was used as the solvent.

Preparation of the Precursor. In a typical procedure, 0.135 g of FeCl3 · 6H2O and 0.08 g of urea were added to 25 mL of ethylene glycol under magnetic stirring. The resultant solution was loaded into a 50 mL Teflon lined stainless steel autoclave, sealed, and heated at 160 °C for 15 h. After the reaction was cooled to room temperature, the green precursor was obtained. The product was collected and washed by centrifugationredispersion cycles with ethanol (approximately 10 mL each time). Please refer to Table 1 for the detailed preparation conditions for typical samples. Preparation of Iron Oxides. The as-prepared precursor (sample 1) was heated in air to 300 °C at a rate of 5 °C min-1 and maintained at this temperature for 1 h to prepare the hollow core/shell hierarchical nanostructures of γ-Fe2O3. The precursor was heated to 300 °C at a rate of 5 °C min-1 and maintained at this temperature for 1 h under the protection of flowing nitrogen gas to prepare the hollow core/shell hierarchical nanostructures of Fe3O4. The reddish brown γ-Fe2O3 and black Fe3O4 powders were obtained, respectively. Preparation of PEG-coated Fe3O4. A 0.025 g sample of the as-prepared hollow core/shell hierarchical nanostructures of Fe3O4 and 0.05 g of PEG-20000 were dissolved in 10 mL of deionized water. The mixture was dispersed by ultrasonic for 10 min. Then, the mixture was kept at 50 °C for 30 min under shaking at a constant rate. The product was separated by centrifugation and washed by deionized water three times and ethanol three times, respectively, in an ultrasonic washer to remove the superfluous PEG, and each time kept for 2 min. Drug loading and in Vitro Drug Release. The typical drug loading and in vitro drug release experiments were performed as follows: 1 g of the PEG-coated Fe3O4 hollow core/shell hierarchical nanostructures was added into 100 mg mL-1 ibuprofen hexane solution. The suspension was shaken in a sealed vessel for 24 h during which the evaporation of hexane was prevented. Then, the PEG-coated Fe3O4 with loaded drug was separated and compacted into disks (each disk 0.3 g) by a pressure of 4 MPa. Each disk was immersed into 200 mL of simulated body fluid (SBF) with pH 7.4 at 37 °C under shaking at a constant rate. The shaking device was a desk-type constanttemperature oscillator (THI-92A, China). The release medium (2 mL) solution was taken out for analysis at given time intervals and replaced with the same volume of fresh preheated SBF (37 °C). The 2.0 mL of extracted medium solution was analyzed by UV-vis absorption spectroscopy at a wavelength of 263 nm. Results and Discussion The detailed preparation conditions and procedures for the samples are described in the Experimental Section, and the preparation conditions for some typical samples are listed in Table 1.

Figure 1. XRD patterns of sample 1 (a), sample 9 (b), γ-Fe2O3 (c), and Fe3O4 (d).

Figure 2. TG and DSC curves of sample 1 (a) and sample 9 (b).

The X-ray powder diffraction (XRD) pattern of the precursor with a green color (sample 1, Figure 1a) shows the crystalline structure of the precursor and the diffraction peaks similar to those of Fe-EG,39 Mn-EG, and Co-EG,40,41 especially the strong peak located in the low-angle region (around 11°). The experiment showed that the precursor could be oxidized in the aqueous solvent, with the green color turning to brown, indicating that the ferrous ions were oxidized to form ferric ions. We propose that Fe3+ ions are reduced by ethylene glycol (EG) molecules to form Fe2+ ions. EG molecules lose protons and the dianions are coordinated with Fe2+ ions. The precursor is possibly a kind of ferrous alkoxide. The thermogravimetric

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Figure 3. SEM micrographs (a-d) and TEM micrograph (e) of the precursor (sample 1).

analysis (TG) and differential scanning calorimetric (DSC) curves of the precursor are shown in Figure 2a, which shows that there is an obvious exothermic peak in the DSC curve and a corresponding sharp mass loss around 274 °C, indicating that the decomposition temperature of the precursor was at around 274 °C. This result also helped us to determine the temperature for the thermal treatment of the precursor. The morphology and microstructure of the precursor were investigated with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Figure 3a-d show the SEM micrographs of the precursor (sample 1), from which one can see hierarchically nanostructured spheres self-assembled by nanosheets. The detailed morphology of the hierarchically nanostructured spheres is shown in Figure 3b-d. The SEM micrograph in Figure 3c indicates the hierarchically nanostructured complex architectures self-assembled by nanosheets with the solid spherical core inside the hollow sphere and circular empty space in between the core and hollow sphere, which is supported by the TEM observation (Figure 3e). The highmagnification SEM micrograph of the sphere surface (Figure 3d) shows that the building blocks of nanosheets were organized to form three-dimensional networks of the shell. These interesting morphological features of the precursor are crucial for its roles as both a source material and a morphological template in the subsequent thermal transformation to γ-Fe2O3, or Fe3O4 with well-preserved similar morphologies. In order to understand the formation mechanism of the precursor with unique hierarchically nanostructured complex architectures, time-dependent experiments were carried out.As shown in Figure 4a-c, nanosheets of the precursor formed at around 2 h and trended to aggregate together. When the solvothermal treatment was conducted for 3 h, the nanosheets aggregated and organized three-dimensionally to form the hierarchically nanostructured spheres (the cores) (Figure 4d-f). When the solvothermal time was increased to 6 h, the hierarchically nanostructured cores assembled by nanosheets became more compact (Figure 4g-i). In the above two stages, the nanosheets in the exterior of the core were packed looser than those in the interior, indicating the density variation of the precursor nanosheets inside the solid cores. Interestingly, as the solvothermal time reached 9 h, the new shell composed of nanosheets formed out of the compact core (Figure 4j-l). The hollow core/shell hierarchical nanostructures of the precursor

formed when the solvothermal time was 12 h (Figure 4m-o). We propose that the evacuation of the solid material occurred by diffusion at a particular region underneath the immediate surface layer, which divided the solid spheres into two discrete regions, resulting in the formation of the circular void space in between the core and the shell. The nanosheets in the exterior of the core dissolved to provide the source material for the formation of the new shell. With increasing solvothermal time, the circular void space in between the core and the shell further expanded, the core and the shell were essentially separated, leaving circular void space in between the core and the shell, forming the unique hollow core/shell hierarchical nanostructures of the precursor, as shown in Figure 3. On the basis of the above experimental results, we propose that the Ostwald ripening involves in the formation mechanism for these novel hierarchically nanostructured complex architectures. It is well-known that the Ostwald ripening process involves “the growth of larger crystals at the expense of smaller ones which have a higher solubility than the larger ones”.42,43 For three-dimensional spheres constructed by nanocrystals, it is comprehensible that the interior void space is eventually generated within the spheres via the Ostwald ripening process, as larger crystals are essentially immobile while the smaller ones are undergoing mass transport through dissolution and regrowth. The ability to form the novel hollow core/shell hierarchical nanostructures can be attributed to the existence of intrinsic density variations inside the starting solid spheres. As discussed above, the exterior of the core is packed much looser than the interior. First, driven by the minimization of the total energy of the system, the nanosheets aggregate and organize to form three-dimensional networked nanostructured spheres, which exhibit different packing densities along the radial direction. The exterior of the sphere with smaller packing densities serve as the starting growth sites for the subsequent recrystallization. As the mass is transported, the void space between the core and the shell is generated through the Ostwald ripening. The formation mechanism for the hollow core/shell hierarchical nanostructures of the precursor is schematically demonstrated in Scheme 1. The effects of the reactant concentration and reaction temperature were also investigated. The nanosheets in the shell were organized more densely as the reactant concentration decreased (Figure 5a-f). Therefore, the density of the shell can be

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Figure 4. SEM micrographs (a, b) and TEM micrograph (c) of sample 2; SEM micrographs (d, e) and TEM micrograph (f) of sample 3; SEM micrographs (g, h) and TEM micrograph (i) of sample 4; SEM micrographs (j, k) and TEM micrograph (l) of sample 5; SEM micrographs (m, n) and TEM micrograph (o) of sample 6.

SCHEME 1: Illustration of the Possible Formation Mechanism for the Hollow Core/Shell Hierarchical Nanostructures of the Precursor via the Ostwald Ripening Process

controlled by adjusting the reactant concentration. The solvothermal temperature has a significant influence on the formation of the product. As discussed above, the novel hollow core/shell hierarchical nanostructures of the precursor formed at 160 °C

for 15 h. However, only dispersed nanosheets formed at 200 °C for 15 h (Figure 5g-i). Several factors, including crystalface attraction, electrostatic and dipolar fields associated with the aggregate, van der Waals forces, and hydrophobic interac-

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Figure 5. (a-c) SEM micrographs of sample 7; (d-f) SEM micrographs of sample 8; (g, h) SEM micrographs and (i) TEM micrograph of sample 9.

tions, may have various effects on the self-assembly.44 Herein, we propose that the viscosity of the reaction system has important effect on the aggregation of nanosheets. As the solvothermal temperature increased to 200 °C (above the boiling point of EG), the viscosity of the reaction system markedly decreased, which made against the aggregation of nanosheets. The XRD pattern (Figure 1b) shows the crystalline and layered structure of the product. The TG and DSC curves of the product (Figure 2b) show that there is an obvious exothermic peak in the DSC curve and a corresponding sharp mass loss at around 288 °C, which is different from the precursor prepared at 160 °C for 15 h (Figures 1a and 2a). On the basis of the preparation of the hollow core/shell hierarchical nanostructures of the precursor, we designed a general thermal transformation strategy to prepare the hollow core/shell hierarchical nanostructures of γ-Fe2O3 and Fe3O4 with well-preserved morphological architectures similar to that of the precursor by using the same precursor (sample 1). When the precursor was heated in air to 300 °C at a rate of 5 °C min-1 and maintained at this temperature for 1 h, the reddish brown product was obtained, and its XRD pattern (Figure 1c) agrees well with the standard XRD pattern of γ-Fe2O3 (JCPDS No. 39-1346). Furthermore, when the precursor was heated to 300 °C at a rate of 5 °C min-1 and maintained at this temperature for 1 h under the protection of flowing nitrogen gas, the black product was obtained, and its XRD pattern (Figure 1d) matches well with the reported data of Fe3O4 (JCPDS No. 85-1436). Moreover, the as-prepared γ-Fe2O3 and Fe3O4 had very similar morphological architectures to that of the precursor, that is to say, the architecture and morphology of the precursor could be well-preserved during the thermal transformation to γ-Fe2O3 and Fe3O4, as demonstrated by the SEM and TEM micrographs in Figure 6a-f. These results indicate that the hollow core/

shell hierarchical nanostructures of γ-Fe2O3 and Fe3O4 can be easily prepared by just using the same hollow core/shell hierarchical nanostructures of the precursor. In addition, the dispersed nannosheets of γ-Fe2O3 and Fe3O4 were also obtained by the thermal decomposition of the corresponding precursor (Figure 6g-j), providing more successful examples for the architecture-preserved precursor transformation strategy. Figure 7 shows the nitrogen adsorption-desorption isotherms and the pore size distributions of the as-prepared hollow core/ shell hierarchical nanostructures of γ-Fe2O3 and Fe3O4, which indicate that the BJH (Barett-Joyner-Halenda) desorption average pore size and the BET surface area were 9.1 nm and 101.7 m2/g for γ-Fe2O3, and 7.1 nm and 113.0 m2/g for Fe3O4, respectively. There existed the nanoporous structures in the hollow core/shell hierarchical nanostructures of both γ-Fe2O3 and Fe3O4. The formation of the nanoporous structures is attributed to the removal of organic species in the hollow core/ shell hierarchical nanostructures of the precursor by pyrolysis. The nanoporous structures provide communicable channels for chemical species traveling between the inner space of the hierarchically nanostructured complex architectures and the outer space of the solution, thus having intriguing applications in a variety of fields. The high specific surface areas of the hollow core/shell hierarchical nanostructures of γ-Fe2O3 and Fe3O4 together with their novel hierarchically nanostructured nanoporous architectures are favorable for their application in drug delivery. The magnetic properties of the hollow core/shell hierarchical nanostructures of Fe3O4 and γ-Fe2O3 were investigated. Parts a and b of Figure 8 show the magnetization curves measured at room temperature for the hollow core/shell hierarchical nanostructures of Fe3O4 and γ-Fe2O3, respectively. Both samples exhibited a superparamagnetic characteristic. The saturation

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Figure 6. Characterization of the as-prepared hollow core/shell hierarchical nanostructures of iron oxides: SEM micrographs (a, b) and TEM micrograph (c) of γ-Fe2O3; SEM micrographs (d, e) and TEM micrograph (f) of Fe3O4. Characterization of dispersed iron oxide nanosheets: SEM micrograph (g) and TEM micrograph (h) of γ-Fe2O3; SEM micrograph (i) and TEM micrograph (j) of Fe3O4.

magnetization of the hollow core/shell hierarchical nanostructures of Fe3O4 and γ-Fe2O3 samples was 50.1 and 34.4 emu/g, respectively, at a magnetic field of 20000 Oe, implying the relatively strong magnetic response to the magnetic field. These saturation magnetization values are much higher than those of the dispersed nanosheets of Fe3O4 (29.0 emu/g) and γ-Fe2O3 (22.2 emu/g) (Figure 8, parts c and d). Poly(ethylene glycol) (PEG) is a kind of neutral, nontoxic, hydrophilic and biocompatible polymer. We used PEG-20000 to modify the hollow core/shell hierarchical nanostructures of Fe3O4 following the procedure reported,39 in order to improve the hydrophilicity and biocompatibility for subsequent drug loading and drug release experiments. The PEG molecule would attach to the anchor to the surface through one of the -OH groups while the other end would provide a polar headgroup to facilitate water solubility. Moreover, the long chains of PEG molecules would improve the stability of the hollow core/shell hierarchical nanostructures of Fe3O4 in aqueous system by stereohindrance effect. We investigated the drug loading and release behaviors of the PEG-coated Fe3O4 hollow core/shell hierarchical nanostructures as the drug carrier. The as-prepared PEG-coated Fe3O4 sample was added into the hexane solution containing ibuprofen

for drug loading. Then, the magnetic PEG-coated Fe3O4 with loaded drug was separated and compacted into disks. The disks were immersed into simulated body fluid (SBF) with pH ) 7.4 under shaking at a constant rate at 37 °C. The release medium solution (2 mL) was taken out for analysis at given time intervals and replaced with the same volume of fresh preheated SBF (37 °C). The UV-vis measurements were performed to analyze the ibuprofen concentrations. As a reference, the drug loading and release behaviors of the uncoated Fe3O4 hollow core/shell hierarchical nanostructures were also investigated. On the basis of the calculation from the standard concentration calibration curve dependent on absorbance of ibuprofen at 263 nm, the ibuprofen storage in the PEG-coated Fe3O4 sample was 643 mg/ g, slightly lower than the value of the uncoated Fe3O4 sample (657 mg/g), indicating the high storage capacity of this drug carrier system for ibuprofen. As discussed above, the as-prepared Fe3O4 samples have nanoporous structures with high specific surface areas. Thus, the ibuprofen molecules should travel through the pores and adsorb on the inner surface of the pore channels and the surface of the nanosheets in both the core and shell to achieve high drug loading capacity. Figure 9 shows the release behaviors of the ibuprofen-PEG-coated Fe3O4 system, ibuprofen-uncoated Fe3O4 system, and pure ibuprofen disk in

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Figure 7. Nitrogen adsorption-desorption isotherms and the pore size distributions of the as-prepared hollow core/shell hierarchical nanostructures of iron oxides: (a, b) γ-Fe2O3; and (c, d) Fe3O4.

the drug release rate of the ibuprofen-uncoated Fe3O4 system (Figure 9b) was higher than that of the ibuprofen-PEG-coated Fe3O4 system (Figure 9a), and about 53% of the loaded drug was released for the first 6 h and 77% for 12 h, and reached a value 86% for 24 h. This experimental result may be explained by the formation of hydrogen bonds between the -OH group of PEG and the -COOH group of ibuprofen molecules in the ibuprofen-PEG-coated Fe3O4 system, leading to slower drug release rate compared with the ibuprofen-uncoated Fe3O4 system. Figure 8. Magnetization curves measured at room temperature for iron oxide samples: (a) hollow core/shell hierarchical nanostructures of Fe3O4; (b) hollow core/shell hierarchical nanostructures of γ-Fe2O3; (c) Fe3O4 dispersed nanosheets; (d) γ-Fe2O3 dispersed nanosheets.

Figure 9. Ibuprofen release curves of the as-prepared samples in SBF: (a) the ibuprofen-PEG-coated Fe3O4 system; (b) the ibuprofen-uncoated Fe3O4 system; (c) the pure ibuprofen disk.

simulated body fluid (SBF). One can see that the release rate of the pure ibuprofen disk was the fastest and the drug release essentially completed within 8 h (Figure 9c). However, the ibuprofen-PEG-coated Fe3O4 system showed the lowest release rate and sustained release of ibuprofen (Figure 9a), which can avoid the explosive release of ibuprofen and prolong the drug effect. One can see that about 43% of the loaded drug was released for the first 6 h and 78% for 24 h, and then the drug release rate decreased and reached a value 87% for 48 h. In contrast,

Conclusion In summary, we have designed and developed a novel method for the preparation of unique nanoporous hollow core/shell hierarchical nanostructures of iron oxide (Fe3O4 or γ-Fe2O3) with a high specific surface area by the solvothermal process (preparation of the precursor) combined with subsequent thermal treatment. The hollow core/shell hierarchical nanostructures of the precursor with a green color can be prepared using nontoxic and inexpensive FeCl3 and urea in ethylene glycol by a surfactant-free solvothermal method at 160 °C for 15 h. We have designed a general thermal transformation strategy to prepare γ-Fe2O3 and Fe3O4 with well-preserved morphological architectures similar to that of the precursor by using the same precursor. The as-prepared γ-Fe2O3 and Fe3O4 have very similar morphological architectures to that of the precursor, that is to say, the architecture and morphology of the precursor can be well-preserved during the thermal transformation to iron oxides (Fe3O4 and γ-Fe2O3). The as-obtained hollow core/shell hierarchical nanostructures of γ-Fe2O3 and Fe3O4 samples have high specific surface areas with the nanoporous structure. The PEGmodified Fe3O4 hollow core/shell hierarchical nanostructures have a high drug loading capacity and favorable drug release property. These hollow core/shell hierarchical nanostructures of iron oxides reported here are very promising for the applications in a variety of fields such as the targeted drug delivery.

12156 J. Phys. Chem. C, Vol. 112, No. 32, 2008 Acknowledgment. Financial support from the National Natural Science Foundation of China (50772124), the Program of Shanghai Subject Chief Scientist (07XD14031), the Key Project for Innovative Research (SCX0606), and the Director Fund of Biomaterials Research Center from Shanghai Institute of Ceramics is gratefully acknowledged. References and Notes (1) Palaniappan, K.; Xue, C.; Arumugam, G.; Hackney, S. A.; Liu, J. Chem. Mater. 2006, 18, 1275. (2) Du, J.; Zhang, J.; Liu, Z.; Han, B.; Jiang, T.; Huang, Y. Langmuir 2006, 22, 1307. (3) Poovarodom, S.; Bass, J. D.; Hwang, S. J.; Katz, A. Langmuir 2005, 21, 12348. (4) Choi, H. J.; Shin, J. H.; Suh, K.; Seong, H. K.; Han, H. C.; Lee, J. C. Nano Lett. 2005, 5, 2432. (5) Wang, Q.; Iancu, N.; Seo, D. K. Chem. Mater. 2005, 17, 4762. (6) Prakash, A.; McCormick, A. V.; Zachariah, M. R. Nano Lett. 2005, 5, 1357. (7) Kim, K.; Webster, S.; Levi, N.; Carroll, D. L.; Pinto, M. R.; Schanze, K. S. Langmuir 2005, 21, 5207. (8) Tang, D. P.; Yuan, R.; Chai, Y. Q. J. Phys. Chem. B 2006, 110, 11640. (9) Xu, Z. C.; Hou, Y. L.; Sun, S. H. J. Am. Chem. Soc. 2007, 129, 8698. (10) (a) Lauhon, L. J.; Gudiksen, M. S.; Wang, D. L.; Lieber, C. M. Nature 2002, 420, 57. (b) Kar, S.; Santra, S.; Heinrich|, H. J. Phys. Chem. C 2008, 112, 4036. (c) Chueh, Y. -L.; Hsieh, C. -H.; Chang, M. -T.; Chou, L. -J.; Lao, C. S.; Song, J. H.; Gan, J.-Y.; Wang, Z. L. AdV. Mater. 2007, 19, 143. (11) Guo, C. W.; Cao, Y.; Xie, S. H.; Dai, W. L.; Fan, K. N. Chem. Commun. 2003, 700. (12) Zhu, L.; Zheng, X.; Liu, X.; Zhang, X.; Xie, Y. J. Colloid Interface Sci. 2004, 273, 155. (13) Zheng, Y. Z.; Cheng, Y.; Wang, Y. S.; Zhou, L. H.; Bao, F. B.; Jia, C. J. Phys. Chem. B 2006, 110, 8284. (14) Hosein, I. D.; Liddell, C. M. Langmuir 2007, 23, 2892. (15) Jia, B. P.; Gao, L. J. Cryst. Growth 2007, 303, 616. (16) Liu, B.; Zeng, H. C. Small 2005, 1, 566. (17) Xu, L. Q.; Zhang, W. Q.; Ding, Y. W.; Yu, W. C.; Xing, J. Y.; Li, F. Q.; Qian, Y. T. J. Cryst. Growth 2004, 273, 213. (18) Zhou, Y.; Yu, S. H.; Wang, C. Y.; Li, X. G.; Zhu, Y. R.; Chen, Z. Y. AdV. Mater. 1999, 11, 850. (19) Cao, M. H.; Liu, T. F.; Gao, S.; Sun, G. B.; Wu, X. L.; Hu, C. W.; Wang, Z. L. Angew. Chem., Int. Ed. 2005, 44, 4197. (20) Chen, X. Y.; Wang, X.; Wang, Z. H.; Yang, X. G.; Qian, Y. T. Cryst. Growth Design 2005, 5, 347.

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