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Preparation of size-controlled (30–100 nm) magnetite nanoparticles for biomedical applications
ARTICLE IN PRESS
Journal of Magnetism and Magnetic Materials 310 (2007) 2408–2410 www.elsevier.com/locate/jmmm
Preparation of size-controlled (30–100 nm) magnetite nanoparticles for biomedical applications K. Nishioa, M. Ikedaa, N. Gokonb, S. Tsubouchia, H. Narimatsua, Y. Mochizukia, S. Sakamotoa, A. Sandhuc, M. Abed, H. Handaa, a
Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan b Department of Advanced Material Science and Engineering Technology, Graduate School of Science and Technology, Niigata University, Niigata, 950-2181, Japan c Department of Electrical and Electronic Engineering, Graduate School of Science and Engineering, Tokyo Institute of Technology, Tokyo 152-8552, Japan d Department of Physical Electronics, Graduate School of Science and Engineering, Tokyo Institute of Technology, Tokyo, 152-8552, Japan Available online 16 November 2006
Abstract Size-controlled magnetite nanoparticles (MNPs) with several dozen nanometers (nm) were synthesized for biomedical applications. Nanoparticles of single-phase magnetite, as revealed by X-ray analyses and magnetic measurements, were prepared by oxidizing ferrous hydroxide (Fe(OH)2) with a weak oxidant NaNO3 in an N2-deaerated aqueous NaOH solution (pH ¼ 12–13) at various temperatures below 37 1C. As the synthesis temperature increases from 4 to 37 1C, the MNPs are decreased in size (d) from 10275.6 to 31.774.9 nm and widened in size distribution, Dd/d increases from 5.5% to 15%. Prepared without using any surfactant, the MNPs are advantageous for immobilizing functional molecules stably on the surfaces for biomedical applications. r 2006 Elsevier B.V. All rights reserved. PACS: 75.50.Tt Keywords: Magnetite nanoparticles (MNPs); Biomedical applications; Size-controlled synthesis
1. Introduction (311)
Intensity (a.u.)
Magnetite (Fe3O4) nanoparticles (MNPs) have been used as magnetic carriers for a variety of biomedical applications [1]. Recently, we have developed magnetic nanobeads with submicron size having a core/shell structure of MNPs (40 nm in size)/polymer for use as magnetic carriers of bioscreening [2]. In order to attain high throughput and high accuracy in bioscreening, the core MNPs must be rather large and their size should be precisely controlled with several dozen nanometers (nm). MNPs synthesized by conventional wet process, well known as co-precipitation method, are smaller than 8 nm and are widely dispersed. Sugimoto and Matijevic [3] synthesized MNPs at 90 1C with regulating their size ranging between 30 and 1.1 mm by a sophisticated chemical route. However, size of their
(220) (400) (111)
E-mail address: [email protected] (H. Handa). 0304-8853/$ - see front matter r 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.jmmm.2006.10.795
(422) (222)
20 Corresponding author. Tel.: +81 45 924 5872; fax: +81 45 924 5145.
(511)
30
40 2 (deg.)
50
60
Fig. 1. XRD diagram for MNPs synthesized at 4 1C.
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ARTICLE IN PRESS K. Nishio et al. / Journal of Magnetism and Magnetic Materials 310 (2007) 2408–2410
MNPs was dispersed with coefficient of variation larger than ca. 15%. Recent progress enabled us to synthesize MNPs with sharp size distribution, but the size has been limited to smaller than 20 nm [4,5]. Since organic solvent and/or surfactant are involved in their methods, organic solvent, and/or surfactant remained on the MNPs surface and tend to make it difficult to encapsulate them in a hydrophilic polymer shell for biomedical use. In this study, we have successfully prepared MNPs with sharply dispersed size ranging between 30 and 100 nm in aqueous solution at relatively low temperatures (4–37 1C) without any surfactant.
Table 1 Size (d (average)7Dd (standard deviation)), size distribution (Dd/d), saturation magnetization (Ms), and residual magnetization (Mr) for magnetite particles at various temperatures T (1C)
Size (nm)
Dd/d
Ms (emu/g)
Mr (emu/g)
4 15 25 37
102.175.6 46.175.3 40.475.7 31.774.9
5.5 11.5 14.1 15.5
91.9 90.2 87.8 81.6
28.5 27.4 31.8 13.0
2409
2. Experimental procedure MNPs were synthesized by surfactant-free oxidation process in an aqueous solution. Into a 21 mM aqueous NaOH solution (475 ml, pH ¼ 12,13), which was sufficiently deaerated by N2 gas, sodium nitrate (NaNO3) (0.75 g, 8.80 mmol) as an oxidant was added. Deaerated 0.1 M ferrous chloride aqueous solution (25 ml) was added to the alkaline solution, which was kept at 4, 15, 25, and 37 1C for 24 h, respectively. MNPs thus synthesized were separated from the solution with a magnet and washed several times with pure water. We investigated the morphology/size, crystal phase, and magnetization for the MNPs using TEM, X-ray diffractometer, and VSM, respectively. 3. Results and discussion As a typical example is shown in Fig. 1, all the synthesized nanoparticles exhibited X-ray diffraction lines ascribed only to the spinel structure. The nanoparticles were essentially magnetite because they had a lattice constant quite near to that reported for bulk Fe3O4. This was also confirmed by their saturation magnetization close
Fig. 2. TEM images for MNPs synthesized at (a) 4 1C, (b) 15 1C, (c) 25 1C, and (d) 37 1C.
ARTICLE IN PRESS 2410
K. Nishio et al. / Journal of Magnetism and Magnetic Materials 310 (2007) 2408–2410
to that (92 emu/g) reported for bulk Fe3O4, as shown in Table 1. All the MNPs had a residual magnetization because their sizes were larger than the superparamagnetic limit (26 nm) of Fe3O4. Table 1 and Fig. 2 show that by increasing the synthesis temperature from 4 to 37 1C leads to a decrease in the MNP’s size (from 10275.6 to 31.7 nm) and changes the MNP’s shape (from octahedral to nearly spherical). Also size distribution of our synthesized MNPs becomes wide, namely Dd/d increases from 5.5% to 15.5%. This indicates that a higher reaction temperature accelerates both nucleation and growth of the magnetite crystals in the aqueous solution. 4. Concluding remarks We succeeded in carrying out the synthesis of strictly size-controlled MNPs (d ¼ 30100 nm and Dd/do15%) by a simple chemical process without any surfactant. Our synthesized MNPs are suitable for coating by functional molecules. Now, we apply these MNPs as a magnetic core for magnetic nanobeads [2] and confirm that prepared
magnetic nanobeads perform a quick and effective responsibility of a magnet. Acknowledgements This work was financially supported by a grant for R&D Projects in Cooperation with Academic Institutions from the New Energy and Industrial Technology Development Organization (NEDO), by a Grant-in-Aid (A) for Scientific Research Priority Areas, No. 18209019, from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), and by Special Coordination Funds for Promoting Science and Technology from MEXT. References [1] H. Urs, S. Wolfgang, T. Joachim, Z. Maciej, in: Scientific and Clinical Applications of Magnetic Carriers, Plenum Press, New York, 1997. [2] H. Handa, K. Nishio, N. Gokon, M. Abe, JP, 2006–88131A. [3] T. Sugimoto, E. Matijevic, J. Colloid Interface Sci. 74 (1980) 227. [4] S. Sun, H. Zeng, D.B. Robinson, S. Raoux, P.M. Rice, S.X. Wang, G. Li, J. Am. Chem. So. 126 (2004) 273. [5] J. Park, K. An, Y. Hwang, J.G. Park, H.J. Noh, J.Y. Kim, J.H. Park, N.M. Hwang, T. Hyeon, Nat. Mater. 3 (2004) 891.
Journal of Magnetism and Magnetic Materials 310 (2007) 2408–2410 www.elsevier.com/locate/jmmm
Preparation of size-controlled (30–100 nm) magnetite nanoparticles for biomedical applications K. Nishioa, M. Ikedaa, N. Gokonb, S. Tsubouchia, H. Narimatsua, Y. Mochizukia, S. Sakamotoa, A. Sandhuc, M. Abed, H. Handaa, a
Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan b Department of Advanced Material Science and Engineering Technology, Graduate School of Science and Technology, Niigata University, Niigata, 950-2181, Japan c Department of Electrical and Electronic Engineering, Graduate School of Science and Engineering, Tokyo Institute of Technology, Tokyo 152-8552, Japan d Department of Physical Electronics, Graduate School of Science and Engineering, Tokyo Institute of Technology, Tokyo, 152-8552, Japan Available online 16 November 2006
Abstract Size-controlled magnetite nanoparticles (MNPs) with several dozen nanometers (nm) were synthesized for biomedical applications. Nanoparticles of single-phase magnetite, as revealed by X-ray analyses and magnetic measurements, were prepared by oxidizing ferrous hydroxide (Fe(OH)2) with a weak oxidant NaNO3 in an N2-deaerated aqueous NaOH solution (pH ¼ 12–13) at various temperatures below 37 1C. As the synthesis temperature increases from 4 to 37 1C, the MNPs are decreased in size (d) from 10275.6 to 31.774.9 nm and widened in size distribution, Dd/d increases from 5.5% to 15%. Prepared without using any surfactant, the MNPs are advantageous for immobilizing functional molecules stably on the surfaces for biomedical applications. r 2006 Elsevier B.V. All rights reserved. PACS: 75.50.Tt Keywords: Magnetite nanoparticles (MNPs); Biomedical applications; Size-controlled synthesis
1. Introduction (311)
Intensity (a.u.)
Magnetite (Fe3O4) nanoparticles (MNPs) have been used as magnetic carriers for a variety of biomedical applications [1]. Recently, we have developed magnetic nanobeads with submicron size having a core/shell structure of MNPs (40 nm in size)/polymer for use as magnetic carriers of bioscreening [2]. In order to attain high throughput and high accuracy in bioscreening, the core MNPs must be rather large and their size should be precisely controlled with several dozen nanometers (nm). MNPs synthesized by conventional wet process, well known as co-precipitation method, are smaller than 8 nm and are widely dispersed. Sugimoto and Matijevic [3] synthesized MNPs at 90 1C with regulating their size ranging between 30 and 1.1 mm by a sophisticated chemical route. However, size of their
(220) (400) (111)
E-mail address: [email protected] (H. Handa). 0304-8853/$ - see front matter r 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.jmmm.2006.10.795
(422) (222)
20 Corresponding author. Tel.: +81 45 924 5872; fax: +81 45 924 5145.
(511)
30
40 2 (deg.)
50
60
Fig. 1. XRD diagram for MNPs synthesized at 4 1C.
70
ARTICLE IN PRESS K. Nishio et al. / Journal of Magnetism and Magnetic Materials 310 (2007) 2408–2410
MNPs was dispersed with coefficient of variation larger than ca. 15%. Recent progress enabled us to synthesize MNPs with sharp size distribution, but the size has been limited to smaller than 20 nm [4,5]. Since organic solvent and/or surfactant are involved in their methods, organic solvent, and/or surfactant remained on the MNPs surface and tend to make it difficult to encapsulate them in a hydrophilic polymer shell for biomedical use. In this study, we have successfully prepared MNPs with sharply dispersed size ranging between 30 and 100 nm in aqueous solution at relatively low temperatures (4–37 1C) without any surfactant.
Table 1 Size (d (average)7Dd (standard deviation)), size distribution (Dd/d), saturation magnetization (Ms), and residual magnetization (Mr) for magnetite particles at various temperatures T (1C)
Size (nm)
Dd/d
Ms (emu/g)
Mr (emu/g)
4 15 25 37
102.175.6 46.175.3 40.475.7 31.774.9
5.5 11.5 14.1 15.5
91.9 90.2 87.8 81.6
28.5 27.4 31.8 13.0
2409
2. Experimental procedure MNPs were synthesized by surfactant-free oxidation process in an aqueous solution. Into a 21 mM aqueous NaOH solution (475 ml, pH ¼ 12,13), which was sufficiently deaerated by N2 gas, sodium nitrate (NaNO3) (0.75 g, 8.80 mmol) as an oxidant was added. Deaerated 0.1 M ferrous chloride aqueous solution (25 ml) was added to the alkaline solution, which was kept at 4, 15, 25, and 37 1C for 24 h, respectively. MNPs thus synthesized were separated from the solution with a magnet and washed several times with pure water. We investigated the morphology/size, crystal phase, and magnetization for the MNPs using TEM, X-ray diffractometer, and VSM, respectively. 3. Results and discussion As a typical example is shown in Fig. 1, all the synthesized nanoparticles exhibited X-ray diffraction lines ascribed only to the spinel structure. The nanoparticles were essentially magnetite because they had a lattice constant quite near to that reported for bulk Fe3O4. This was also confirmed by their saturation magnetization close
Fig. 2. TEM images for MNPs synthesized at (a) 4 1C, (b) 15 1C, (c) 25 1C, and (d) 37 1C.
ARTICLE IN PRESS 2410
K. Nishio et al. / Journal of Magnetism and Magnetic Materials 310 (2007) 2408–2410
to that (92 emu/g) reported for bulk Fe3O4, as shown in Table 1. All the MNPs had a residual magnetization because their sizes were larger than the superparamagnetic limit (26 nm) of Fe3O4. Table 1 and Fig. 2 show that by increasing the synthesis temperature from 4 to 37 1C leads to a decrease in the MNP’s size (from 10275.6 to 31.7 nm) and changes the MNP’s shape (from octahedral to nearly spherical). Also size distribution of our synthesized MNPs becomes wide, namely Dd/d increases from 5.5% to 15.5%. This indicates that a higher reaction temperature accelerates both nucleation and growth of the magnetite crystals in the aqueous solution. 4. Concluding remarks We succeeded in carrying out the synthesis of strictly size-controlled MNPs (d ¼ 30100 nm and Dd/do15%) by a simple chemical process without any surfactant. Our synthesized MNPs are suitable for coating by functional molecules. Now, we apply these MNPs as a magnetic core for magnetic nanobeads [2] and confirm that prepared
magnetic nanobeads perform a quick and effective responsibility of a magnet. Acknowledgements This work was financially supported by a grant for R&D Projects in Cooperation with Academic Institutions from the New Energy and Industrial Technology Development Organization (NEDO), by a Grant-in-Aid (A) for Scientific Research Priority Areas, No. 18209019, from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), and by Special Coordination Funds for Promoting Science and Technology from MEXT. References [1] H. Urs, S. Wolfgang, T. Joachim, Z. Maciej, in: Scientific and Clinical Applications of Magnetic Carriers, Plenum Press, New York, 1997. [2] H. Handa, K. Nishio, N. Gokon, M. Abe, JP, 2006–88131A. [3] T. Sugimoto, E. Matijevic, J. Colloid Interface Sci. 74 (1980) 227. [4] S. Sun, H. Zeng, D.B. Robinson, S. Raoux, P.M. Rice, S.X. Wang, G. Li, J. Am. Chem. So. 126 (2004) 273. [5] J. Park, K. An, Y. Hwang, J.G. Park, H.J. Noh, J.Y. Kim, J.H. Park, N.M. Hwang, T. Hyeon, Nat. Mater. 3 (2004) 891.