Polycation Hybrid Capsules

Feb 3, 2011 - The present Article describes the synthesis of ferromagnetic capsules approximately 330 nm in diameter with a nanometer-thick shell to a...
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Ferromagnetic FePt-Nanoparticles/Polycation Hybrid Capsules Designed for a Magnetically Guided Drug Delivery System Teruaki Fuchigami,† Ryo Kawamura,† Yoshitaka Kitamoto,*,† Masaru Nakagawa,‡ and Yoshihisa Namiki§ †

Department of Innovative and Engineered Materials, Tokyo Institute of Technology, J2-40, 4259 Nagatsuta, Midori-ku, Yokohama 226-8502, Japan ‡ Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan § Institute of Clinical Medicine and Research, The Jikei University School of Medicine, Kashiwa-shita, Kashiwa, Chiba 277-8567, Japan

bS Supporting Information ABSTRACT: The present Article describes the synthesis of ferromagnetic capsules approximately 330 nm in diameter with a nanometer-thick shell to apply to magnetic carriers in a magnetically guided drug delivery system. The magnetic shell of 5 nm in thickness is a nanohybrid, composed of ordered alloy FePt nanoparticles of approximately 3-4 nm in size and a polymer layer of a cationic polyelectrolyte, poly(diaryldimethylammonium chloride) (PDDA). The magnetic capsules have an excellent capacity for carrying medical drugs and genes. Surface-modified silica particles with PDDA were used as a template for the capsules. FePt nanoparticles were deposited on the PDDA-modified silica particles through a polyol method followed by dissolving the silica particles with a NaOH solution, resulting in the formation of the magnetic capsules as the final product. A three-dimensional hollow structure is maintained by the nanohybrid shell. The FePt-nanoparticles/PDDA nanohybrid shell also exhibits a ferromagnetic feature at room temperature because the FePt nanoparticles of an ordered-alloy phase are formed with the aid of PDDA despite the small size (3-4 nm).

’ INTRODUCTION Drug delivery systems (DDSs) are one of the crucial components of cancer therapy techniques that effectively work on tumors when they achieve both pinpoint precision and minimal invasion. Magnetically guided DDSs, in particular, have great potential for enhancing the accumulation of drug agents in tumors.1-3 There are two ways to use magnetic carriers, as follows: (1) filling magnetic capsules with the drug and (2) adsorbing the drug outside the magnetic particle(s). The former method is superior to the latter in terms of avoiding loss by elution in the bloodstream during the delivery of water-soluble drugs. This feature is advantageous for the further development of the DDS because the majority of intravenous injection drugs are hydrophilic. Thus, magnetic capsules are more widely applicable as a magnetic carrier, compared with magnetic particles. Studies on hollow microspheres composed of a Fe3O4 shell have already been reported.4-12 The hollow microspheres were fabricated by depositing Fe3O4 on template particles made of polystyrene (PS), silica, or melamine-formaldehyde alternately coated with poly(sodium p-styrenesulfonate) and poly(allyamine hydrochloride), followed by removal of the template particles.4-6 The thickness of the Fe3O4 magnetic shell was approximately 20 nm or greater; the Fe3O4 shell was a polycrystalline layer composed of crystallites or nanoparticles of approximately 20 nm in size. The maximum size applicable in an intravenous infusion DDS is reported to be approximately 400 nm.13,14 Thus, the loading r 2011 American Chemical Society

capacity for the drug is limited to 70% of the volume of a hollow microsphere when using a DDS particle with a diameter of 350 nm and a magnetic shell thickness of 20 nm. A thinner magnetic shell composed of magnetic nanoparticles is required to increase the loading capacity of medicine and to decrease the quantity of magnetic components administered into human bodies under the limitation of size applicable to the DDS. However, the size of Fe3O4 nanoparticles forming the magnetic shell is required to be 20 nm or more so as to be magnetically directed by a rare-earth permanent magnet such as a NdFeB magnet, considering the magnetocrystalline anisotropy constant of Fe3O4 (∼104 J m-3). If a magnetic material with a magnetocrystalline anisotropy constant higher than that of Fe3O4 is applicable, the shell thickness and/or the nanoparticle size will be reduced without any inappropriate deterioration of the magnetic response. An FePt alloy exhibits an order-disorder transformation; its magnetocrystalline anisotropy constant (105-106 J m-3) is higher than that of Fe3O4 and increases with the increase of the atomic-order parameter.15 Chemical syntheses of FePt nanoparticles that exhibit ferromagnetic features at 300 K have been reported.16-18 Our previous reports demonstrated that a certain water-soluble polymer, poly(N-vinyl-2-pyrrolidone) (PVP), was Received: October 12, 2010 Revised: December 18, 2010 Published: February 03, 2011 2923

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Figure 1. Fabrication scheme of a FePt-nanoparticles/PDDA/silica composite particle and a magnetic capsule.

effective in synthesizing ordered-alloy FePt nanoparticles;19-21 the FePt nanoparticles of 3-4 nm in diameter displayed ferromagnetic features at 300 K. It appears that the polymer provides nucleation sites for the ordered-alloy FePt nanoparticles. In the present study, we demonstrate that magnetic capsules with a nanometer-thick magnetic shell will be fabricated by growing the ordered-alloy FePt nanoparticles on silica template particles of which the anionic surface is modified with a cationic polymer poly(diaryldimethylammonium chloride) (PDDA), followed by the removal of the silica template particles with an alkaline aqueous solution. Interestingly, the polymer single layer adsorbed on the silica particles became the base structure of the shell, and provided nucleation sites for growing the ordered-alloy FePt nanparticles in a hybrid manner. The situation allowed us to fabricate the three-dimensional ferromagnetic capsules. The hollow structure with a PDDA single-layer integrating the FePt nanoparticles was maintained even after the removal of the silica template particles, similar to hollow microspheres composed of an alternate polycation/polyanion multilayer.22 The magnetic hybrid shell composed of FePt nanoparticles and polycation PDDA had a thickness of approximately 5 nm. The loading capacity was estimated to reach 92% of the hybrid capsule volume in the case of a DDS particle which was 350 nm in diameter. Magnetic capsules with a nanometer-thick hybrid shell composed of FePt nanoparticles and PDDA were fabricated according to the scheme shown in Figure 1. First, negatively charged silica template particles were modified with cationic PDDA in deionized water. FePt nanoparticles which were 3-4 nm in diameter were selectively grown on the surfaces of the PDDAmodified silica particles by a polyol-reduction method,16-21 resulting in the formation of FePt-nanoparticles/PDDA/silica composite particles. Magnetic capsules with a FePt-nanoparticles/PDDA magnetic hybrid shell were obtained by dissolving the silica template particles using an aqueous solution of NaOH. The capsular size and morphology are tunable in terms of choosing the size of the silica template particles. Amorphous silica particles were useful for the chemical synthesis of FePt nanoparticles and for their removal with an alkaline aqueous solution because of their high thermal stability and facile dissolubility into an alkaline aqueous solution.

’ EXPERIMENTAL SECTION An aqueous dispersion (5 mL) of amorphous silica particles (80 mg, Nippon Shokubai, KE-P30, average diameter = 0.32 μm) was mixed with an aqueous solution (24 mL) of PDDA (0.29 g, Sigma-Aldrich, weightaverage molecular weight (Mw) < 100 kg mol-1). This mixture was stirred for 10 min at 298 K in an ultrasonic bath. PDDA-modified silica particles were purified to remove excess PDDA by washing three times by means of centrifugation with deionzed water, removal of supernatant, and redispersion using an ultrasoic bath. In addition, two kind of silica

template particles such as unmodified and surfactant-treated silica particles were used for the templates of the composite particles. The surfactant-treated silica particles were prepared by immersing silica particles in an ethanol solution (29 mL) containing oleic acid (145 mg) and oleylamine (145 mg), followed by washing three times in a similar manner. Then we obatained three kind of templates such as unmodified silica particles, PDDA-modified silica particles, and silica particles treated with oleic acid and oleylamine surfactants. Each silica template particle (40 mg) was dispersed in tetraethylene glycol (TEG) (50 mL) after solvent exchange by centrifugation. Then FePt nanoparticles were synthesized through the following polyol method.19,20 A mixture of Fe(III) acetylacetonate (0.21 mmol, 75 mg), Pt(II) acetylacetonate (0.19 mmol, 76 mg), each silica template particle (40 mg), and TEG (50 mL) was placed in a 100 mL three-necked, round-bottom flask. The reaction flask was fitted to a mantle heater. The mixture was stirred and then heated with stirring from 300 K at a heating rate of 10 K min-1 and kept at 503 or 533 K by refluxing for 2 h in an inert gas (Ar/ H2). Fe(III) acetylacetonate and Pt(II) acetylacetonate as metallic precursors were reduced in TEG as a reducing reagent. After the reaction, the solution was cooled to room temperature. The composite silica particles were precipitated by centrifugation. After discarding the light brown supernatant, the precipitate was washed several times with ethanol. The three kinds of composite silica partilces were obtained by centrifuging and drying in air at room temperature as powder samples. The template silica particles were dissolved by stirring in a 3 mol dm-3 NaOH aqueous solution which included the composite particles at 343 K for 1 h. Then the specimens were purified by several times of centrifugation and redispersion using an ultrasonic bath in deionized water. Finally, the magnetic capsules were obtained by centrifugation and drying in air at room temperature until powder samples were obtained. The crystal structure of the composite particles and magnetic capsules was investigated using a powder X-ray diffractometer (Rigaku, RINT 2100V). The size and morphology of the synthesized samples were observed using a transmission electron microscope (Hitachi, H-8100). Magnetic properties were measured using a Physical Property Measurement System (Quantum Design, PPMS) at 5-320 K.

’ RESULTS AND DISCUSSION FePt nanoparticles were synthesized at 503 K in the presence of silica particles with an average diameter of 320 nm. Figure 2a-c shows transmission electron microscope (TEM) images of FePt nanoparticles synthesized on three kinds of silica template particles, which were unmodified silica particles, PDDA-modified silica particles, and silica particles treated with oleic acid and oleylamine surfactants, respectively. The surfactants oleic acid and oleylamine were used because FePt nanoparticles are typically synthesized in the presence of such low-molecular-weight surfactants.18 The PDDA-modified silica template particles were entirely covered with FePt nanoparticles as shown in Figure 2b, whereas the unmodified silica template 2924

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Figure 2. TEM images of (a-c) silica particles coated with FePt nanoparticles prepared at 503 K and (d, e) magnetic capsules with a FePtnanoparticles/PDDA hybrid shell after dissolving the silica template particles: (a) FePt nanoparticles formed on a bare silica particle, (b) FePt nanoparticles formed on a PDDA-modified silica particle, and (c) FePt nanoparticles formed on a silica particle treated with oleic acid and oleylamine surfactants.

particles were partially covered with FePt nanoparticles as shown in Figure 2a. The silica template particles treated with the oleic acid and oleylamine surfactants were also entirely covered with FePt nanoparticles as shown in Figure 2c. These results suggested that FePt nanoparticles accumulated to the organic compounds which were used in synthesizing FePt nanoparticles. Thus, the presence of the organic compounds on the surface of silica template particles played an important role in the formation of the composite particles. It was evident in the magnified TEM images that there was no significant difference in size and shape among these FePt nanoparticles; the diameter of the FePt nanoparticles was 3-4 nm. As another morphological feature, aggregates of FePt nanoparticles were observed outside the silica template particles as seen in Figure 2a and c. It was obvious that FePt nanoparticles were preferentially formed on PDDA, oleic acid, and oleylamine. The aggregates seen in Figure 2c were deduced to have been formed with the aid of the oleic acid and oleylamine molecules, which exhibited a reversible adsorption manner during the nanoparticle synthesis. Hollow microspheres with a FePt-nanoparticles/PDDA hybrid shell, referred to as “magnetic capsules”, were successfully obtained by dissolving the silica template particles from the FePtnanoparticles/PDDA/silica nanocomposite particles (Figure 2b) in a NaOH aqueous solution. Figure 2d shows a TEM image of the magnetic capsules. The magnetic capsules had an average diameter of 330 nm. Therefore, the thickness of the hybrid shell was calculated to be approximately 5 nm from the diameter of the silica particles (320 nm). Although almost all the magnetic capsules were spherical, ruptured capsules were also observed.

Several deformed hollow microspheres were observed as shown in Figures 2e and f, probably because the TEM observations were performed in a vacuum. These results suggest that PDDA molecules were not dissolved by washing with a NaOH aqueous solution and easily shaped hybrid shells composed of FePt nanoparticles and flexible PDDA molecules were formed. Thus, these magnetic capsules exhibited flexibility in an aqueous solution. As shown in Figure 2d, the three-dimensional structure of the magnetic capsules was maintained after removal of the template silica particles with a NaOH aqueous solution. In contrast, any magnetic capsules were hardly obtained after dissolving the template particles in a similar manner from the composite FePt-nanoparticles and silica particles treated with the lowmolecular-weight surfactants. It was supposed that the threedimensional structure of the magnetic capsules was maintained with the aid of PDDA, which had a strong binding force to the FePt nanoparticles, because there was no bond among the FePt nanoparticles themselves. Whereas a 111 diffraction peak with the strongest intensity at 2θ = 41° and diffraction peaks at 2θ = 24° and 33° are observed for an ordered-alloy fct (face-centered tetragonal) FePt, a 111 diffraction peak with the strongest intensity at 2θ = 40° is observed without diffraction peaks at 2θ = 24° and 33° for a disordered-alloy fcc (face-centered cubic) FePt; the 111 diffraction peak shifts from 40° to 41° with the increase of the orderedalloy phase.15 The three different types of the composite particles containing FePt nanoparticles and silica particles shown in Figure 2a-c exhibited the typical X-ray diffraction (XRD) 2925

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Table 1. Crystallite Size and Blocking Temperature of FePt Nanoparticles Which Were Formed on Bare Silica Particles (FePt/Silica), Surfactant-Treated Silica Particles (FePt/Oleic Acid and Oleylamine/Silica), PDDA-Modified Silica Particles (FePt/PDDA/Silica), and Magnetic Capsules after Dissolving the Silica Template Particles (FePt/PDDA) synthesis

crystallite

blocking

temperature (K)

size (nm)

temperature (K)

FePt/silica

503

2.4

80

FePt/oleic acid and

503

2.0

40

FePt/PDDA/silica

503

2.4

180

FePt/PDDA/silica

533

3.5

above 320

FePt/PDDA

533

3.5

above 320

material

oleylamine/ silica

pattern of FePt (see the Supporting Information). Although the 111 diffraction peak was observed between 40° and 41° for all of the composite particles, diffraction peaks at 24° and 33° were not confirmed probably due to their small crystallites. Therefore, it was difficult to determine whether the FePt nanoparticles in the composite particles prepared at 503 K had a fct structure from only the XRD patterns. The crystallite sizes were calculated according to Sherrer’s formula and are summarized in Table 1. The crystallite sizes of FePt nanoparticles synthesized at 503 K were 2.0-2.4 nm, and there was not a significant difference in size among them. To evaluate magnetic properties of the composite particles shown in Figure 2a-c, zero-field-cooled (ZFC) alternate current (AC) magnetic susceptibility was measured at 10 Hz in the temperature range of 5-320 K, and zero-field-cooled (ZFC) and field-cooled (FC) direct current (DC) magnetization was also measured at 100 Oe in the same temperature range. The imaginary part of the AC susceptibility χ00 takes a maximum value at a certain temperature (see the Supporting Information), which is defined as the blocking temperature related to a thermal relaxation of the magnetization. The blocking temperature of magnetic nanoparticles is proportional to the product of a magnetocrystalline anisotropy constant and a volume of the nanoparticles if the magnetic interactions between the nanoparticles are negligibly small. The blocking temperatures of the composite particles are also summarized in Table 1. FePt nanoparticles on unmodified silica particles, PDDA-modified silica particles, and surfactant-treated silica particles prepared at 503 K showed a blocking temperature of 80, 180, and 40 K, respectively (Supporting Information). The blocking temperature of the FePt nanoparticles on the PDDA-modified silica particles was 4.5 times as high as that on the silica particles treated with oleic acid and oleylamine surfactants. The volume of the FePt nanoparticles in the former was estimated to be approximately 1.7 times as large as that of the latter because the crystallite sizes were 2.4 nm for the former and 2.0 nm for the latter. Therefore, the magnetocrystalline anisotropy constant of the FePt nanoparticles formed on the PDDA-modified silica template particles was 2.6 times as high as that of the FePt nanoparticles on the silica template particles treated with oleic acid and oleylamine surfactants, suggesting that the FePt nanoparticles formed on the PDDA-modified silica template particles at the reaction temperature of 503 K had a fct structure. PDDA would have a significant effect on promoting the atomic ordering

Figure 3. Powder XRD patterns of (a) FePt-nanoparticles/PDDA/ silica composite particles and (b) magnetic capsules after dissolving the silica particles from the composite particles. The insets are the XRD patterns enlarged in the vicinity of 2θ = 25°. The composite particles were prepared at 533 K. The arrow indicates the 001 diffraction peak at approximately 2θ = 24°.

in the FePt nanoparticles compared with oleic acid and oleylamine surfactants. To increase the crystallite size and promote the transition from a disordered-alloy fcc to an ordered-alloy fct structure in FePt nanoparticles, the integration of FePt nanoparticles on PDDA-modified silica particles was carried out at the higher temperature of 533 K. Figure 3 shows XRD patterns of the (a) FePt-nanoparticles/PDDA/silica composite particles prepared at 533 K and (b) magnetic capsules after template removal with a NaOH aqueous solution. There was no clear difference between the two XRD patterns; a broad 001 peak was observed at approximately 2θ = 24° as shown in the insets of Figure 3. These XRD patterns clearly show that the FePt nanoparticles on the PDDA layer had a fct structure, which is the atomically ordered phase. The crystallite size was calculated to be 3.5 nm, which was larger than that observed for the FePt nanoparticles prepared at 503 K (2.4 nm). The blocking temperatures of the FePtnanoparticles/PDDA/silica composite particles and FePt-nanoparticles/PDDA nanohybrid shells were increased from 180 K to above 320 K by raising the synthesizing temperature from 503 to 533 K as summarized in Table 1. Figure 4 shows ZFC and FC curves of DC magnetization measured at 100 Oe for the FePt-nanopartilces/PDDA/silica composite particles prepared at 533 K and the magnetic capsules. Interestingly, the ZFC magnetization curves of the FePt nanoparticles included in both the composite particles and the magnetic capsules did not show a peak, indicating that the blocking temperature was above 320 K.These results indicate that the magnetic shell prepared at 533 K exhibited ferromagnetic features even at approximately body temperature. There were no changes in the temperature dependences of DC magnetization except for the values of the magnetization; the dissolution of the silica template particles was demonstrated by the increase of the magnetization after the alkali treatment. The FePt-nanoparticles/PDDA hybrid shell was not affected by dissolving the silica template particles with a NaOH aqueous solution as supported by Figures 3 and 4 indicating their crystallographic and magnetic properties. We considered two models for the formation of the FePtnanoparticles/PDDA hybrid shell, which displayed a high durability to a NaOH alkaline aqueous solution of high ion strength. 2926

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In the case of magnetically guided DDS, the nanometer-thick magnetic shell is advantageous for a dramatic enhancement of the drug loading capacity and a reduction in the magnetic components administered. Magnetic properties, such as magnetic susceptibility and the blocking temperature, are manipulated with maintaining the shell thickness at approximately 5 nm through varying the synthesis temperature. The diameter of the magnetic capsules would be easily controlled by changing the size of the silica template particles.

’ ASSOCIATED CONTENT

bS

Supporting Information. XRD patterns (Figure S1) and temperature dependence of the AC magnetic susceptibility of the composite particles (Figure S2). This material is available free of charge via the Internet at http://pubs.acs.org.

Figure 4. ZFC and FC temperature-dependence of DC magnetization measured at 100 Oe for FePt-nanoparticles/PDDA/silica composite particles which were synthesized at 533 K and FePt-nanoparticles/ PDDA magnetic capsules after dissolving the silica template particles.

The models are as follows : (1) FePt nanoparticles grow on and/ or in a PDDA single-layer on a silica particle and (2) FePt nanoparticles which are formed in a reaction solution are adsorbed on a PDDA single-layer. The composite particles could not be obtained from the unmodified silica particles as shown in Figure 1a. There were differences in the crystallite size and the blocking temperature for the three different composite particles listed in Table 1. These phenomena support the former model because if FePt nanoparticles adsorbed on organic compounds after the nanoparticle growth, there should not be significant differences in magnetic properties of composite particles prepared using three kinds of surface-modified silica particles. It is obvious that the organic compounds on the silica template particles’ surface were effective in the formation of the inorganic-organic hybrid structures, and that the cationic polymer PDDA played an important role in the growing and crystallization of the FePt nanoparticles with an ordered-alloy phase. When the quantity of the FePt nanoparticles which were formed on the PDDA-modified silica particles was reduced, the FePt nanoparticles were scattered into the suspension and the magnetic capsules were not obtained after dissolving the silica particles. This result shows that the three-dimensional structure of the magnetic capsules was maintained by cooperation between the FePt nanoparticles and PDDA, and also suggests that the FePt nanoparticles growing on the PDDA layer bound the polymer chains and the nanohybrid structure stabilized the three-dimensional structure, leading to the formation of the nanocomposite shell of the magnetic capsules.

’ CONCLUSIONS This study demonstrates the formation of ferromagnetic capsules of approximately 330 nm in diameter with an ultrathin shell, which were designed to be magnetic carriers in magnetically guided DDS. The 5 nm thick magnetic shell was a nanohybrid composed of ordered-alloy FePt nanoparticles of approximately 3-4 nm in size and a single-layer of a cationic polyelectrolyte, PDDA. The magnetic capsules were fabricated by depositing FePt nanoparticles on silica template particles modified with PDDA by a polyol method, followed by dissolving the silica template particles. The magnetic capsules exhibited ferromagnetic features at approximately body temperature.

’ AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected]. Telephone: þ81-45-9245424. Fax: þ81-45-924-5433.

’ ACKNOWLEDGMENT This work was supported by an Industrial Technology Research Grant, Program 08C46049a (2008), from the New Energy and Industrial Technology Development Organization (NEDO) of Japan and by Grant-in-Aid for Scientific Research #20310077 from Japan Society for the Promotion of Science (JSPS). ’ REFERENCES (1) Namiki, Y.; Namiki, T.; Yoshida, H.; Ishii, Y.; Tsubota, A.; Koido, S.; Narial, K.; Mitsunaga, M.; Yanagisawa, S.; Kashiwagi, H.; Mabashi, Y.; Yumoto, Y.; Hoshina, S.; Fujise, K.; Tada, N. Nat. Nanotechnol. 2009, 202, 1–9. (2) Pankhurst, Q. A.; Connolly, J.; Jones, S. K.; Dobson, J J. Phys. D: Appl. Phys. 2003, 36, 167–180. (3) Hirota, Y.; Akiyama, Y.; Izumi, Y.; Nishijima, S. Phys. C 2009, 469, 1853–1856. (4) Lu, Z.; Qin, Y.; Fang, J.; Sun, J.; Li, J.; Liu, F.; Yang, W. Nanotechnology 2008, 19, 055602–055606. (5) Nakamura, M.; Katagiri, K.; Koumoto, K. J. Colloid Interface Sci. 2010, 341, 64–68. (6) Abe, M.; Nishio, N.; Hatakeyama, M.; Hanyu, N.; Tanaka, T.; Tada, M.; Nakagawa, T.; Sandhu, A.; Handa, H. J. Magn. Magn. Mater. 2009, 321, 645–649. (7) Liu, J.; Deng, Y.; Liu, C.; Sun, Z.; Zhao, D. J. Colloid Interface Sci. 2009, 333, 329–334. (8) Shen, S.; Wu, W.; Guo, K.; Meng, H.; Chen, J. Colloids Surf., A 2007, 311, 99–105. (9) Xia, H.; Foo, P.; Yi, J. Chem. Mater. 2009, 21, 2442–2451. (10) Lu, X.; Mao, H.; Zhang, W. Polym. Composites 2009, 847–854. (11) Wang, C.; Chen, I.; Lin, C. J. Magn. Magn. Mater. 2006, 304, 451–453. (12) Yang, S.; Liu, H.; Huang, H.; Zhang, Z. J. Colloid Interface Sci. 2009, 338, 584–590. (13) Yuan, F.; Dellian, M.; Fukumura, D.; Leunig, M.; Berk, D. A.; Torchilin, V. O.; Jain, R. K. Cancer Res. 1995, 55, 3752–3756. (14) Maeda, H.; Bharate, G. Y.; Daruwalla, J. Eur. J. Pharm. Biopharm. 2009, 71, 409–419. (15) Sakuma, H.; Taniyama, T.; Ishii, K.; Kitamoto, Y.; Yamazaki, Y. J. Magn. Magn. Mater. 2006, 300, 284–292. 2927

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