- Nano Express
- Open Access
Preparation of hollow magnetite microspheres and their applications as drugs carriers
© Márquez et al; licensee Springer. 2012
- Received: 12 December 2011
- Accepted: 10 April 2012
- Published: 10 April 2012
Hollow magnetite microspheres have been synthesized by a simple process through a template-free hydrothermal approach. Hollow microspheres were surface modified by coating with a silica nanolayer. Pristine and modified hollow microparticles were characterized by field-emission electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, FT-IR and Raman spectroscopy, and VSM magnetometry. The potential application of the modified hollow magnetite microspheres as a drug carrier was evaluated by using Rhodamine B and methotrexate as model drugs. The loading and release kinetics of both molecules showed a clear pH and temperature dependent profile.
Hollow magnetite microspheres have been synthesized. Load-release experiments with Rhodamine-B as a model drug and with Methotrexate (chemotherapy drug used in treating certain types of cancer) demonstrated the potential applications of these nanostructures in biomedical applications.
- Drug carrier
During the last few years, magnetic oxides particles [1–3] have attracted a great deal of attention due to their interesting applications in different fields such as catalysis [4, 5], information storage , optoelectronics [7, 8], and biomedical applications that include magnetic bioseparation, magnetic resonance imaging contrast enhancement, and targeted drug [9–18]. Among these magnetic materials, magnetic hollow structures with dimensions ranging from the nanometer to micrometer scale are of potential use for controlled release and drug delivery [19, 20]. Up to date, syntheses including the use of templates are well known as very effective approaches to achieve hollow structures [21–28]. Nevertheless, these procedures involve tedious synthesis steps and normally have economic drawbacks. Over the past recent years, different template-free synthesis methods have been tested with very interesting results. Thus, Zhu et al. have synthesized monodisperse magnetite hollow microspheres with diameters ranging from 200 to 300 nm and shell thickness of ca. 50 nm by using a free-template solvothermal procedure . In a recent paper, we synthesized monodisperse hollow magnetite microspheres by a one-step process through a template-free hydrothermal approach employing FeCl3 and ferrocene as precursor and propylene glycol-isopropanol as solvent . These materials are characterized by having a large surface area, a very low density, and also a strong magnetic response that make them interesting candidates to be used as drug carriers. The internal hollow spaces may be used as hosts for the encapsulation of guest molecules or specific drugs. However, the use of these nanostructured materials has some limitations arising from the tendency to aggregation because of their high specific area and strong interparticle interactions . To overcome this drawback, different strategies for the chemical stabilization of the naked hollow magnetite have been tested, including the incorporation of polymer structures on the magnetite surface or the amine functionalization of the hollow magnetite surface [31, 32].
All reagents used in the present investigation were of analytical grade. FeCl3 anhydrous (99.98%), propylene glycol and diethyl amine were provided by Fisher Scientific (Pittsburgh, PA, USA) and used as received. Rhodamine B and methotrexate were provided by Merck Chemicals (Beeston, Nottingham, UK) and used without further purification. Pure ethyl alcohol and tetraethyl orthosilicate (TEOS) were provided by Aldrich Chemical Co. MilliQ (St. Louis, MO, USA)water (18.2 MΩ.cm at 25°C) was used for all experiments.
Synthesis of hollow magnetic Fe3O4 microspheres
For a typical synthesis, 2 mmol of FeCl3 were dissolved in 10 mL of propylene glycol; the solution was magnetically stirred at room temperature for 10 min followed by soft ultrasonic treatment for 5 min. Next, 1 mmol of ferrocene was added, and the solution was stirred at room temperature for 2 h. Finally, 3 mL of diethyl amine were added to the mixture. The solution was placed into the Teflon-lined stainless steel autoclave of 30 mL capacity and maintained at 180°C for 24 h. Lower synthesis temperatures (100 to 150°C) were tested although the synthesized hollow magnetite microspheres were not stable, and the degradation was produced in a few days, generating compact magnetite nanoparticles of no more than 10 nm diameter. The use of FeCl3/ferrocene as precursor is required to induce a faster self-assembling of nanoparticles into hollow microspheres.
After cooling to room temperature, the black sediment is collected and washed in water by five centrifugation (6,000 rpm, 10 min)-redispersion cycles. Next, the black sediment was resuspended in ethanol and washed by two centrifugation (6,000 rpm, 5 min)-redispersion cycles. Finally, the microspheres were suspended in ethanol and dried overnight at 60°C. Hollow Fe3O4 microspheres were maintained in sealed containers before characterization.
Preparation of magnetic SiO2@Fe3O4 microspheres
The silica shell has been prepared by using a modified Stobe-Fink-Bohn method [33, 34], which consists of two steps: (i) the hydrolysis of TEOS (Si(C2H5O)4) in ethanol, in presence of ammonium hydroxide as catalyst, and (ii) the polymerization phase, where the siloxane (Si-O-Si) bonds are formed and anchored on the hollow magnetite surface. In a typical synthesis, 50 mg of hollow Fe3O4 microspheres were added to 20 mL of ethanol. The mixture was homogenized in an ultrasound bath for 10 min. Next, 0.5 mL of deionized water and 0.5 mL of ammonium hydroxide (36%) were added into the flask under vigorous mechanical stirring to prevent particles from settling. Temperature was termostatized at 20°C for at least 20 min, and after this period, 0.5 mL of TEOS was added dropwise to the reaction mixture over the course of 5 min under constant stirring in fumehood. After addition, reaction mixture was vigorously stirred for 30 min. Next, the solvent of the reaction mixture is evaporated at 60°C overnight. The residue is washed twice in distilled water and finally in ethanol and allowed to dry in vacuum at room temperature.
Encapsulation efficacy within hollow microparticles
To evaluate the potential application of these hollow spheres as drug carriers, three different infiltrations of an organic compound were tested. Rh-B was chosen as test molecule for different reasons. First of all, the size of this molecule is not too small (as occurs with the most of drugs used for therapeutic treatments). On the other hand, this compound is soluble in polar solvents and shows a very high fluorescence quantum yield that can be useful to evidence the presence of very low amounts of this compound, even at trace levels. In this way, Rh-B at three different concentrations (0.05, 0.1, and 0.2 mg/mL) in ethanol were prepared. The infiltration consisted in adding the appropriate amount of Rh-B solution into an erlenmeyer flask containing 5 mg of hollow particles. This mix was mechanically stirred, and the result for each Rh-B concentration was evaluated at different time period, namely 1, 2, 4, 6, 8, 9, and 12 h. These infiltrations were developed at 20°C and 40°C. After infiltration, the particles were centrifuged (1,000 rpm, 5 min) and washed three times with MilliQ water. The particles loads with Rh-B were dried overnight at 60°C. To determine the amount of Rh-B storage in the hollow microspheres, thermogravimetry (TG) was employed to directly measure the weight loss of as-prepared product.
The release kinetics was studied in aqueous solution by controlling the pH and temperature of the solvent by the dialysis bag method. The dialysis bag was soaked in water for 3 h before use. The dialysis bag retained the magnetite microspheres allowing free Rh-B to diffuse into the solution of study. To monitor the Rh-B release by pH and temperature effect, solutions at different times were analyzed by fluorescence spectroscopy. The pH of solution was adjusted using acetate 0.01 M (pH = 3.7) and phosphate 0.01 M (pH = 7.4) buffers. All load and release tests developed on Rh-B were also tested on MTX, a drug used in some cancer treatments.
X-ray powder diffraction patterns (XRD) were collected using an X'Pert PRO X-ray diffractometer (PANalytical, The Netherlands) in Bragg-Brentano goniometer configuration. The X-ray radiation source was a ceramic X-ray diffraction Cu anode tube type Empyrean of 2.2 kW.
Raman spectra were collected using a micro-Raman Renishaw RM2000 single grating spectrograph, equipped with 532 and 785 nm excitation sources. Raman spectra were acquired in the spectral range of 3,200-100 cm-1. The acquisition time for each measurement was 20 s and a defocused laser power level in the range of 10 to 60 mW was used to prevent the possible thermal effects on the samples. Infrared spectra were obtained in the 4,000-400 cm-1 region by using a Bruker Optics IFS 66 series FT-IR spectrometer (Bruker Optik Gmbh, Ettlingen, Germany). The variation in magnetization and coercivity of the hollow magnetite samples was determined by using a Lake Shore-7400 vibrating sample magnetometer (VSM) (Lake Shore Cryotronics Inc, Westerville, OH, USA) at room-temperature.
Field emission scanning electron microscopy (FE-SEM) images were obtained using a JEOL JM-6400 microscope. High Resolution Transmission electron microscopy (HRTEM) images were recorded on a JEOL 3000 with an acceleration voltage of 300 kV.
X-ray photoelectron spectroscopy (XPS) measurements were performed on an ESCALAB 220i-XL spectrometer (VG-Scientific, East Grinstead, UK, by using the non-monochromated Mg Ka (1,253.6 eV) radiation of a twin-anode, operating at 20 mA and 12 kV in the constant analyzer energy mode, with a PE of 50 eV. In order to remove charging shifts and deal with Fermi edge coupling problems, binding energies were corrected using the peak of the C-(C, H) component coming from contamination carbon (set to 284.6 eV). The samples were pressed on to a molybdenum support in an argon-filled glove box and then were put into the preparation chamber to pump for approximately 24 h at 60°C under a pressure of about 10-7 Pa to minimize surface contamination. Small amounts of activated carbon fine powder were added to the samples to improve their conductivity. The vacuum during spectra acquisition was better than 5 × 10-9 mbar.
TG analysis data were obtained with a TGA Q-500 instrument (TA Instruments)under inert atmosphere of nitrogen at a heating rate of 20°C min-1, from 100 to 600°C. The specific surface area, the pore volume, and the pore size distribution of the hollow magnetite microspheres, were measured using a Micromeritics ASAP 2020. The micropore volume, WMP [cm2/g], was measured using the Barrett-Joyner-Halenda (BJH) approach .
Characterization of magnetite microspheres
Hollow magnetite microspheres can easily be dispersed in water even though the sedimentation is produced in a short time (typically no more than 15 min). Silica-coated hollow magnetite microspheres previously dispersed in water form a permanent suspension that can be separated from the solvent by applying an external magnetic field. The magnetic particles can be brought back into the original solution by removing the external magnetic field and gently shaking the solution.
The Brunauer-Emmett-Teller surface area and pore parameters of the synthesized samples were determined by N2 adsorption-desorption isotherm measurement at 77 K. Pristine hollow microspheres have a surface area of ca. 50 m2 g-1, while silica-coated hollow microspheres show a slightly lower 46 m2 g-1. The pore size distributions were determined using the Barrett-Joyner-Halenda calculations  on the desorption portion of the isotherm at 77 K revealing a narrow distribution centered at 3.2 and 2.4 nm for pristine and coated microspheres, respectively. This result agrees with the fact that microspheres are composed by smaller nanoparticles organized to form hollow spheres allowing the existence of pores with nanometric dimensions.
Loading and release of test molecules
In the present work, we have synthesized hollow magnetite microspheres by a simple one-step hydrothermal procedure. With the aim to increase the solubility in polar solvents, these microspheres were subsequently surface modified by growing a silica nanolayer via sol-gel process. The potential application of the modified hollow magnetite microspheres as a drug carrier was evaluated by using Rh-B and MTX as model drugs. The loading and release kinetics of both molecules experienced a pH and temperature dependent profile. It is expected that this dependency could be modified and selected for specific functions, opening up promising applications in biomedical fields.
The authors gratefully recognize the financial support provided by the Department of Energy through the Massey Chair project at University of Turabo and from the National Science Foundation through the contract CHE-0959334. Financial support from MICINN (Spain) through the grant MAT2010-19804 is also acknowledged. The "Servicio Interdepartamental de Investigación (SIdI)" from Universidad Autónoma de Madrid and "Centro de Microscopía Luis Bru" from Universidad Complutense de Madrid are acknowledged for the use of the FE-SEM and HRTEM facilities. OPP also acknowledges the support from The National Science Foundation under Grant No. HRD 0833112 (CREST program).
- Yu D, Sun X, Zou J, Wang Z, Wang F, Tang K: Oriented assembly of Fe3O4nanoparticles into monodisperse hollow single-crystal microspheres. J Phys Chem B 2008, 110: 21667–21671.View ArticleGoogle Scholar
- Deng H, Li X, Peng Q, Wang X, Chen J, Li Y: Monodisperse magnetic single-crystal ferrite microspheres. Angewandte Chemie Int Ed 2005, 44: 2782–2785. 10.1002/anie.200462551View ArticleGoogle Scholar
- Lu AH, Salabas EL, Schuth F: Magnetic nanoparticles: synthesis, protection, functionalization, and application. Angewandte Chemie Int Ed 2007, 46: 1222–1244. 10.1002/anie.200602866View ArticleGoogle Scholar
- Escobar GP, Beroy AQ, Iritia MPP, Huerta JH: Kinetic study of the combustion of methyl-ethyl ketone over a-hematite catalyst. Chem Eng J 2004, 102: 107–117. 10.1016/j.cej.2003.09.006View ArticleGoogle Scholar
- Werner W, Wolfgang R: Surface chemistry and catalysis on well-defined epitaxial iron-oxide layers. Prog Surf Sci 2002, 70: 1–151. 10.1016/S0079-6816(01)00056-9View ArticleGoogle Scholar
- Black CT, Murray CB, Sandstrom RL, Sun S: Spin-dependent tunneling in self-assembled cobalt-nanocrystal superlattices. Science 2000, 290: 1131–1134. 10.1126/science.290.5494.1131View ArticleGoogle Scholar
- Zeng H, Li J, Liu JP, Wang ZL, Sun SH: Exchange-coupled nanocomposite magnets by nanoparticle self-assembly. Nature 2002, 420: 395–398. 10.1038/nature01208View ArticleGoogle Scholar
- Tiwari S, Choudhary RJ, Phase DM: Effect of growth temperature on the structural and transport properties of magnetite thin films prepared by pulse laser deposition on single crystal Si substrate. Thin Solid Films 2009, 517: 3253–3256. 10.1016/j.tsf.2008.11.074View ArticleGoogle Scholar
- Min JY, Kim ST, Lee JS, Kim K, Wu JH, Jeong J, Song AY, Lee KM, Kim YK: "Labeling of macrophage cell using biocompatible magnetic nanoparticles". J Appl Phys 2011, 109: 07B309–1-07B309–3. 10.1063/1.3563073View ArticleGoogle Scholar
- Lou L, Yu K, Zhang Z, Li B, Zhu J, Wang Y, Huang R, Zhu Z: Functionalized magnetic-fluorescent hybrid nanoparticles for cell labeling. Nanoscale 2011, 3: 2315–2323. 10.1039/c1nr10066aView ArticleGoogle Scholar
- Laurent N, Sapet C, Gourrierec LL, Bertosio E, Zelphati O: Nucleic acid delivery using magnetic nanoparticles: the Magnetofection™ technology. Ther Delivery 2011, 2: 471–482. 10.4155/tde.11.12View ArticleGoogle Scholar
- Liu F, Laurent S, Fattahi H, Elst VL, Muller RN: Superparamagnetic nanosystems based on iron oxide nanoparticles for biomedical imaging. Nanomedicine 2011, 6: 519–528. 10.2217/nnm.11.16View ArticleGoogle Scholar
- Silva AC, Oliveira TR, Mamani JB, Malheiros SMF, Malavolta L, Pavon LF, Sibov TT, AmaroJr E, Tannús A, Vidoto ELG, Martins MJ, Santos RS, Gamarra LF: Application of hyperthermia induced by superparamagnetic iron oxide nanoparticles in glioma treatment. Int J Nanomed 2011, 6: 591–603.Google Scholar
- Hafeli UO, Riffle JS, Shekhawat LH, Baranauskas AC, Mark F, Dailey JP, Bardenstein D: Cell uptake and in vitro toxicity of magnetic nanoparticles suitable for drug delivery. Mol Pharmaceutics 2009, 6: 1417–1428. 10.1021/mp900083mView ArticleGoogle Scholar
- Guo M, Que C, Wang C, Liu X, Yan H, Liu K: Multifunctional superparamagnetic nanocarriers with folate-mediated and pH-responsive targeting properties for anticancer drug delivery. Biomaterials 2011, 32: 185–194. 10.1016/j.biomaterials.2010.09.077View ArticleGoogle Scholar
- Liang G, Cai S, Zhang P, Peng Y, Chen H, Zhang S, Kong J: Magnetic relaxation switch and colorimetric detection of thrombin using aptamer-functionalized gold-coated iron oxide nanoparticles. Anal Chim Acta 2011, 689: 243–249. 10.1016/j.aca.2011.01.046View ArticleGoogle Scholar
- Martina MS, Fortin JP, Menager C, Clement O, Barratt G, Grabielle-Madelmont C, Gazeau F, Cabuil V, Lesieur S: Generation of superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging. J Am Chem Soc 2005, 127: 10676–10685. 10.1021/ja0516460View ArticleGoogle Scholar
- Frey NA, Peng S, Cheng K, Sun S: Magnetic nanoparticles: synthesis, functionalization, and applications in bioimaging and magnetic energy storage. Chem Soc Rev 2009, 38: 2532–2542. 10.1039/b815548hView ArticleGoogle Scholar
- Liu S, Xing R, Lu F, Rana RK, Zhu JJ: One-Pot template-free fabrication of hollow magnetite nanospheres and their application as potential drug carriers. J Phys Chem 2009, 113: 21042–21047.Google Scholar
- Márquez F, Campo T, Cotto M, Polanco R, Roque R, Fierro P, Sanz JM, Elizalde E, Morant C: Synthesis and characterization of monodisperse magnetite hollow microspheres. Soft Nanosci Lett 2011, 1: 25–32. 10.4236/snl.2011.12005View ArticleGoogle Scholar
- Fan HJ, Gosele U, Zacharias M: Formation of nanotubes and hollow nanoparticles based on kirkendall and diffusion processes: a review. Small 2007, 3: 1660–1671. 10.1002/smll.200700382View ArticleGoogle Scholar
- Kim D, Park J, An K, Yang NK, Park JG, Hyeon T: Synthesis of hollow iron nanoframes. J Am Chem Soc 2007, 129: 5812–5813. 10.1021/ja070667mView ArticleGoogle Scholar
- Hu P, Yu L, Zuo A, Guo C, Yuan F: Fabrication of monodisperse magnetite hollow spheres. J Phys Chem C 2009, 113: 900–906. 10.1021/jp806406cView ArticleGoogle Scholar
- Wang X, Yuan FL, Hu P, Yu LJ, Bai L: Self-assembled growth of hollow spheres with octahedron-like Co nanocrystals via one-pot solution fabrication. J Phys Chem C 2008, 112: 8773–8778. 10.1021/jp0775404View ArticleGoogle Scholar
- Yu DB, Sun XQ, Zou JW, Wang ZR, Wang F, Tang K: Oriented assembly of Fe3O4nanoparticles into monodisperse hollow single-crystal microspheres. J Phys Chem B 2006, 110: 21667–21671. 10.1021/jp0646933View ArticleGoogle Scholar
- Lee D, Cohen RE, Rubner MF: Heterostructured magnetic nanotubes. Langmuir 2007, 23: 123–129. 10.1021/la0612926View ArticleGoogle Scholar
- Ye QL, Kozuka Y, Yoshikawa H, Awaga K, Bandow S, Iijima S: Effects of the unique shape of submicron magnetite hollow spheres on magnetic properties and domain states. Phys Rev B 2007, 75: 224404–224408.View ArticleGoogle Scholar
- Lu LT, Tung LD, Long J, Fernig DJ, Thanh NTK: Facile synthesis of stable, water-soluble magnetic Copt hollow nanostructures assisted by multi-thiol ligands. J Mat Chem 2009, 19: 6023–6028. 10.1039/b906839bView ArticleGoogle Scholar
- Zhu LP, Xiao HM, Zhang WD, Yang G, Fu SY: "One-pot template-free synthesis of monodisperse and single-crystal magnetite hollow spheres by a simple solvothermal route" cryst. Growth Des 2008, 8: 957. 10.1021/cg700861aView ArticleGoogle Scholar
- Deng YH, Wang CC, Hu JH, Yang WL, Fu SK: Investigation of formation of silica-coated magnetite nanoparticles via Sol-Gel approach. Coll Surf A: Physicochem Eng Aspects 2005, 262: 87–93. 10.1016/j.colsurfa.2005.04.009View ArticleGoogle Scholar
- Das M, Dhak P, Gupta S, Mishra D, Maiti TK, Basak A, Pramanik P: Highly biocompatible and water-dispersible, amine functionalized magnetite nanoparticles, prepared by a low temperature, air-assisted polyol process: a new platform for bio-separation and diagnostics. Nanotechnology 2010, 21: 125103–125109. 10.1088/0957-4484/21/12/125103View ArticleGoogle Scholar
- Wu W, He Q, Jiang C: Magnetic iron oxide nanoparticles: synthesis and surface functionalization strategies. Nanoscale Res Lett 2008, 3: 397–415. 10.1007/s11671-008-9174-9View ArticleGoogle Scholar
- Stobe W, Fink A, Bohn E: Controlled growth of monodisperse silica spheres in the micron size range. J Coll Int Sci 1968, 26: 62. 10.1016/0021-9797(68)90272-5View ArticleGoogle Scholar
- Márquez F, Roque R: Synthesis and characterization of large specific surface area nanostructured amorphous silica materials. J Nanosci Nanotechnol 2006, 6: 1114–1118. 10.1166/jnn.2006.166View ArticleGoogle Scholar
- Barrett EP, Joyner LG, Halenda PP: The determination of pore volume and area distributions in porous substances. I. Computations from nitrogen isotherms. J Am Chem Soc 1951, 73: 373–380. 10.1021/ja01145a126View ArticleGoogle Scholar
- Laurent S, Forge D, Port M, Roch A, Robic C, Vander Elst L, Muller RN: Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem Rev 2008, 108: 2064–2110. 10.1021/cr068445eView ArticleGoogle Scholar
- Guan N, Wang Y, Sun D, Xu J: A simple one-pot synthesis of single-crystalline magnetite hollow spheres from a single iron precursor. Nanotechnology 2009, 20: 105603–8pp. 10.1088/0957-4484/20/10/105603View ArticleGoogle Scholar
- Xi GC, Wang C, Wang X: The oriented self-assembly of magnetic Fe3O4nanoparticles into monodisperse microspheres and their use as substrates in the formation Of Fe3O4nanorods. Eur J Inorg Chem 2008, 3: 425–431.View ArticleGoogle Scholar
- Zeng SY, Tang KB, Li TW, Liang ZH, Wang D, Wang YK, Zhou W: Hematite hollow spindles and microspheres: selective synthesis, growth, mechanisms, and application in Liion battery and water treatment. J Phys Chem C 2007, 111: 10217–10225. 10.1021/jp0719661View ArticleGoogle Scholar
- Wang LY, Luo J, Fan Q, Suzuki M, Engelhard MH, Lin Y, Kim N, Wang JQ, Zhong C: Monodispersed Core/Shell Fe3O4@Au nanoparticles. J Phys Chem B 2005, 109: 21593–21601. 10.1021/jp0543429View ArticleGoogle Scholar
- Teng X, Black D, Watkins N, Gao Y, Yang H: Platinum-maghemite core/shell nanoparticles using a sequential synthesis. Nano Lett 2003, 3: 261–264. 10.1021/nl025918yView ArticleGoogle Scholar
- Schwertmann U, Cornell RM: "The iron oxides". New York: VCH; 1996.Google Scholar
- Shebanova ON, Lazor PJ: Raman spectroscopic study of magnetite (FeFe2O4): a new assignment for the vibrational spectrum. J Solid State Chem 2003, 174: 424–430. 10.1016/S0022-4596(03)00294-9View ArticleGoogle Scholar
- De Faria DLA, Silva SV, De Oliveira MT: Raman microspectroscopy of some iron oxides and oxyhydroxides. J Raman Spectrosc 1997, 28: 873–878. 10.1002/(SICI)1097-4555(199711)28:11<873::AID-JRS177>3.0.CO;2-BView ArticleGoogle Scholar
- Ma M, Zhang Y, Yu W, Shen HY, Zhang HQ, Gu N: Preparation and characterization of magnetite nanoparticles coated by amino silane. Coll Surf A Physicochem Eng Aspects 2003, 212: 219–226. 10.1016/S0927-7757(02)00305-9View ArticleGoogle Scholar
- Nakata N, Hu Y, Uzun O, Bakr O, Stellacci F: Chains of superparamagnetic nanoparticles. Adv Mater 2008, 20: 4294. 10.1002/adma.200800022View ArticleGoogle Scholar
- Nagao D, Yokoyama M, Yamauchi N, Matsumoto H, Kobayashi Y, Konno M: Synthesis of highly monodisperse particles composed of a magnetic core and fluorescent shell. Langmuir 2008, 24: 9804–9808. 10.1021/la801364wView ArticleGoogle Scholar
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