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Toxicity estimation of magnetic fluids in a biological test
ARTICLE IN PRESS
Journal of Magnetism and Magnetic Materials 304 (2006) e406–e408 www.elsevier.com/locate/jmmm
Toxicity estimation of magnetic fluids in a biological test S.I. Parka, J.H. Limb, J.H. Kimc, H.I. Yunb, C.O. Kima,c, a
Department of Materials Science and Engineering, Chungnam National University, 305-764 Daejeon, Korea Division of Veterinary Pharmacology and Toxicology, Chungnam National University, 305-764 Daejeon, Korea c Research Center for Advanced Magnetic Materials, Chungnam National University, 305-764 Daejeon, Korea
b
Available online 3 March 2006
Abstract Uniform magnetic nanoparticles were prepared by chemical coprecipitation. Decanoic acid was used as the first surfactant to minimize the magnetic dipole–dipole interaction, and starch, citric acid, decanoic acid, polyethylene glycol and alginic acid were selected as the second surfactants for hydrophilicity. The applied second surfactants strongly influenced the biological toxicity of the magnetic particles as well as the properties of magnetic fluids. r 2006 Elsevier B.V. All rights reserved. Keywords: Coprecipitation; Magnetic fluid; Nanoparticle; Surfactant; Toxicity
1. Introduction There are currently 70 different species of magnetic fluid [1–4]. The magnetic fluid consists of ultrafine magnetic particles and dispersion medium, and the disperser is mostly classified with an oxide system and a metal system. In general, the preparation process of nanosized shapes (nanoparticles, nanotubes, nanolayers) is an important part in their structural and chemical properties [5]. The technology of modern nanomaterials is being developed for special applications. The property of related material for cancer therapeutics of humans needs to be more comprehended, and the technique for cancer treatment must be successfully applied to destroy only cancer cells without damaging the normal cells [6]. The required properties of magnetic fluids for biomedical applications contain the particle size suitable for injection into the body and discharge, the high saturation magnetization for drug delivery and the adsorption of surfactants for the inhibition of agglomeration between the particles. Especially, when the biocompatible molecule is introduced in the second surfactant, the toxicity of magnetic particles in a body can be inhibited [7]. Therefore, the second surfactant was Corresponding author. Tel.: +82 42 821 6233; fax: +82 42 822 6272.
E-mail address: [email protected] (C.O. Kim). 0304-8853/$ - see front matter r 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.jmmm.2006.01.205
selected as a parameter in the preparation of magnetic fluids, and the toxicity of each magnetic fluid was biologically estimated. 2. Experimental Magnetic particles were synthesized by chemical coprecipitation and magnetic fluids were prepared by dispersing the particles with bilayed surfactants into water. Ferric chloride hexahydrate (FeCl3 6H2O, 499%) and ferrous chloride tetrahydrate (FeCl2 4H2O, 499%) were used as an Fe source and ammonium hydroxide (NH4OH, 499%) as an alkali source, and the stirring was continuously carried out to 80 1C. In order to minimize the dipole–dipole reaction between magnetic particles, decanoic acid was adsorbed onto the particles as the first surfactant, and starch, citric acid, decanoic acid, polyethylene glycol (PEG) and alginic acid were applied as the second surfactants [8]. The prepared samples were centrifugally separated at conditions of 60 1C and 70 cmHg with a vacuum drier for the measurement of the particle properties. The magnetization of magnetic particles was measured in a field range from 10 kOe to +10 kOe by VSM (LDJ9600). The morphology and size of the magnetic particles were observed by TEM (TECNAIF 20). After 0.1%, 0.5% and
ARTICLE IN PRESS S.I. Park et al. / Journal of Magnetism and Magnetic Materials 304 (2006) e406–e408
1.0% of the prepared samples for total blood amount which corresponded to 0.1, 0.5 and 1.0 ml of magnetic fluid, respectively, were intravenously injected in 6–7-weekold male Sprague–Dawley rats weighing 190–220 g, the toxicity was estimated.
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3. Results and discussion Figs. 1(a) and (b) show micrographs of the magnetic fluids with citric acid- and alginic acid-adsorbed magnetic particles, respectively. The particle size distribution is shown in a histogram in Fig. 1(c). For particle sizes between 6 and 12 nm, the mean size was 8.5 nm. The size distribution was similar in all the samples. These particle sizes were in good agreement with results calculated by VSM [9]. The shape of the particles was nearly spherical and their phase was mostly Fe3O4.
Fig. 2. Auto-optical opinion of a lung after injection of magnetic fluid 1.0% for total blood volume into the vein of a Sprague–Dawley rat. Table 1 Mortality of rat in intravenous injection of magnetic fluids with different second surfactants Surfactant group
Fig. 1. TEM micrographs for magnetic particles with bilayers of (a) decanoic acid/citric acid and (b) decanoic acid/alginic acid, and (c) their size distribution.
Decanoic Decanoic Decanoic Decanoic Decanoic
acid–starch acid–citric acid acid–decanoic acid acid–PEG acid–alginic acid
Mortality (%) 0.1%
0.5%
1.0%
0 0 0 0 0
10 0 10 10 0
100 0 100 100 0
ARTICLE IN PRESS e408
S.I. Park et al. / Journal of Magnetism and Magnetic Materials 304 (2006) e406–e408
The superparamagnetism was apparently observed in all magnetic fluids at room temperature. The saturation magnetization 60 emu/g for the magnetic particles with decanoic acid and PEG surfactants was significantly less than the saturation value of 92 emu/g of bulk magnetite [10]. Finite-size effects have been reported as being responsible for the reduction in the saturation magnetization of nanoparticles [11]. The reduction in the saturation magnetization of Fe3O4 spinel can be attributed to the presence of nonmagnetic layer on particles, cation distribution, superparamagnetic relaxation and spin canting because of unique properties of the ultrafine material. In the same process, the difference in saturation magnetization for each fluid sample was not so significant. Therefore, the toxicity may be the more important parameter for application of hydrophilic magnetic fluids. The toxicity result of the magnetic fluids in a biological test of rat is represented with different surfactant groups in Table 1. The fluids with citric acid and alginic acid as second surfactants caused only a weak pulse in the injection of 1.0% (1 ml of magnetic fluid) for total blood amount. However, in the other surfactant groups, the symptoms such as difficulty in breathing and a weak pulse appeared even with injection of 0.1% of magnetic fluid for total blood amount. Also, the injection of 1.0% for total blood amount resulted in the death of all animals. Figs. 2(a) and (b) show the reddish brown lung of a dead animal and its magnified view, respectively. The actual microscopic observation revealed that the magnetic particles were incorporated in the capillary blood vessels. 4. Conclusions In case of decanoic acid–citric acid or decanoic acid–alginic acid as surfactants of magnetic particles for
the hydrophilic magnetic fluids in an animal experiment, the symptom such as only a weak pulse appeared without dead animals. Therefore, if the surface properties are more improved and the injection amount is more properly selected, excellent applicability for cancer treatment is expected.
Acknowledgements This study was supported by the Korea Science and Engineering Foundation through the Research Center for Advanced Magnetic Materials at Chungnam National University.
References [1] A. Hu¨tten, D. Sudfeld, I. Ennen, G. Reiss, K. Wojczykowski, P. Jutzi, J. Magn. Magn. Mater. 293 (2005) 93. [2] I. Nakatani, M. Hijikata, K. Ozawa, J. Magn. Magn. Mater. 122 (1993) 10. [3] K. Raj, R. Moskowitz, J. Magn. Magn. Mater. 85 (1990) 233. [4] F. Elias, C. Flament, Phy. Rev. E 56 (1991) 3310. [5] D.K.Kim, Nanoparticles: engineering, assembly, and biomedical applications, Ph.D. Thesis, MATCHEM, MET, KTH, 2002. [6] R. Hiergeist, W. Andra¨, N. Buske, R. Hergt, I. Hilger, U. Richter, W. Kaiser, J. Magn. Magn. Mater. 201 (1999) 420. [7] Z.G.M. Lacava, R.B. Azevedo, E.V. Martins, L.M. Lacava, J. Magn. Magn. Mater. 201 (1999) 431. [8] S.I. Park, J.H. Lim, J.H. Kim, J.S. Roh, C.G. Kim, C.O. Kim, Phys. Stat. Sol. (b) 241 (2004) 1662. [9] D.K. Kim, Y. Zhang, J. Magn. Magn. Mater. 225 (2001) 30. [10] D.H. Han, J.P. Wang, H.L. Luo, J. Magn. Magn. Mater. 136 (1994) 176. [11] J.M.D. Coey, Phys. Rev. Lett. 27 (1971) 1140.
Journal of Magnetism and Magnetic Materials 304 (2006) e406–e408 www.elsevier.com/locate/jmmm
Toxicity estimation of magnetic fluids in a biological test S.I. Parka, J.H. Limb, J.H. Kimc, H.I. Yunb, C.O. Kima,c, a
Department of Materials Science and Engineering, Chungnam National University, 305-764 Daejeon, Korea Division of Veterinary Pharmacology and Toxicology, Chungnam National University, 305-764 Daejeon, Korea c Research Center for Advanced Magnetic Materials, Chungnam National University, 305-764 Daejeon, Korea
b
Available online 3 March 2006
Abstract Uniform magnetic nanoparticles were prepared by chemical coprecipitation. Decanoic acid was used as the first surfactant to minimize the magnetic dipole–dipole interaction, and starch, citric acid, decanoic acid, polyethylene glycol and alginic acid were selected as the second surfactants for hydrophilicity. The applied second surfactants strongly influenced the biological toxicity of the magnetic particles as well as the properties of magnetic fluids. r 2006 Elsevier B.V. All rights reserved. Keywords: Coprecipitation; Magnetic fluid; Nanoparticle; Surfactant; Toxicity
1. Introduction There are currently 70 different species of magnetic fluid [1–4]. The magnetic fluid consists of ultrafine magnetic particles and dispersion medium, and the disperser is mostly classified with an oxide system and a metal system. In general, the preparation process of nanosized shapes (nanoparticles, nanotubes, nanolayers) is an important part in their structural and chemical properties [5]. The technology of modern nanomaterials is being developed for special applications. The property of related material for cancer therapeutics of humans needs to be more comprehended, and the technique for cancer treatment must be successfully applied to destroy only cancer cells without damaging the normal cells [6]. The required properties of magnetic fluids for biomedical applications contain the particle size suitable for injection into the body and discharge, the high saturation magnetization for drug delivery and the adsorption of surfactants for the inhibition of agglomeration between the particles. Especially, when the biocompatible molecule is introduced in the second surfactant, the toxicity of magnetic particles in a body can be inhibited [7]. Therefore, the second surfactant was Corresponding author. Tel.: +82 42 821 6233; fax: +82 42 822 6272.
E-mail address: [email protected] (C.O. Kim). 0304-8853/$ - see front matter r 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.jmmm.2006.01.205
selected as a parameter in the preparation of magnetic fluids, and the toxicity of each magnetic fluid was biologically estimated. 2. Experimental Magnetic particles were synthesized by chemical coprecipitation and magnetic fluids were prepared by dispersing the particles with bilayed surfactants into water. Ferric chloride hexahydrate (FeCl3 6H2O, 499%) and ferrous chloride tetrahydrate (FeCl2 4H2O, 499%) were used as an Fe source and ammonium hydroxide (NH4OH, 499%) as an alkali source, and the stirring was continuously carried out to 80 1C. In order to minimize the dipole–dipole reaction between magnetic particles, decanoic acid was adsorbed onto the particles as the first surfactant, and starch, citric acid, decanoic acid, polyethylene glycol (PEG) and alginic acid were applied as the second surfactants [8]. The prepared samples were centrifugally separated at conditions of 60 1C and 70 cmHg with a vacuum drier for the measurement of the particle properties. The magnetization of magnetic particles was measured in a field range from 10 kOe to +10 kOe by VSM (LDJ9600). The morphology and size of the magnetic particles were observed by TEM (TECNAIF 20). After 0.1%, 0.5% and
ARTICLE IN PRESS S.I. Park et al. / Journal of Magnetism and Magnetic Materials 304 (2006) e406–e408
1.0% of the prepared samples for total blood amount which corresponded to 0.1, 0.5 and 1.0 ml of magnetic fluid, respectively, were intravenously injected in 6–7-weekold male Sprague–Dawley rats weighing 190–220 g, the toxicity was estimated.
e407
3. Results and discussion Figs. 1(a) and (b) show micrographs of the magnetic fluids with citric acid- and alginic acid-adsorbed magnetic particles, respectively. The particle size distribution is shown in a histogram in Fig. 1(c). For particle sizes between 6 and 12 nm, the mean size was 8.5 nm. The size distribution was similar in all the samples. These particle sizes were in good agreement with results calculated by VSM [9]. The shape of the particles was nearly spherical and their phase was mostly Fe3O4.
Fig. 2. Auto-optical opinion of a lung after injection of magnetic fluid 1.0% for total blood volume into the vein of a Sprague–Dawley rat. Table 1 Mortality of rat in intravenous injection of magnetic fluids with different second surfactants Surfactant group
Fig. 1. TEM micrographs for magnetic particles with bilayers of (a) decanoic acid/citric acid and (b) decanoic acid/alginic acid, and (c) their size distribution.
Decanoic Decanoic Decanoic Decanoic Decanoic
acid–starch acid–citric acid acid–decanoic acid acid–PEG acid–alginic acid
Mortality (%) 0.1%
0.5%
1.0%
0 0 0 0 0
10 0 10 10 0
100 0 100 100 0
ARTICLE IN PRESS e408
S.I. Park et al. / Journal of Magnetism and Magnetic Materials 304 (2006) e406–e408
The superparamagnetism was apparently observed in all magnetic fluids at room temperature. The saturation magnetization 60 emu/g for the magnetic particles with decanoic acid and PEG surfactants was significantly less than the saturation value of 92 emu/g of bulk magnetite [10]. Finite-size effects have been reported as being responsible for the reduction in the saturation magnetization of nanoparticles [11]. The reduction in the saturation magnetization of Fe3O4 spinel can be attributed to the presence of nonmagnetic layer on particles, cation distribution, superparamagnetic relaxation and spin canting because of unique properties of the ultrafine material. In the same process, the difference in saturation magnetization for each fluid sample was not so significant. Therefore, the toxicity may be the more important parameter for application of hydrophilic magnetic fluids. The toxicity result of the magnetic fluids in a biological test of rat is represented with different surfactant groups in Table 1. The fluids with citric acid and alginic acid as second surfactants caused only a weak pulse in the injection of 1.0% (1 ml of magnetic fluid) for total blood amount. However, in the other surfactant groups, the symptoms such as difficulty in breathing and a weak pulse appeared even with injection of 0.1% of magnetic fluid for total blood amount. Also, the injection of 1.0% for total blood amount resulted in the death of all animals. Figs. 2(a) and (b) show the reddish brown lung of a dead animal and its magnified view, respectively. The actual microscopic observation revealed that the magnetic particles were incorporated in the capillary blood vessels. 4. Conclusions In case of decanoic acid–citric acid or decanoic acid–alginic acid as surfactants of magnetic particles for
the hydrophilic magnetic fluids in an animal experiment, the symptom such as only a weak pulse appeared without dead animals. Therefore, if the surface properties are more improved and the injection amount is more properly selected, excellent applicability for cancer treatment is expected.
Acknowledgements This study was supported by the Korea Science and Engineering Foundation through the Research Center for Advanced Magnetic Materials at Chungnam National University.
References [1] A. Hu¨tten, D. Sudfeld, I. Ennen, G. Reiss, K. Wojczykowski, P. Jutzi, J. Magn. Magn. Mater. 293 (2005) 93. [2] I. Nakatani, M. Hijikata, K. Ozawa, J. Magn. Magn. Mater. 122 (1993) 10. [3] K. Raj, R. Moskowitz, J. Magn. Magn. Mater. 85 (1990) 233. [4] F. Elias, C. Flament, Phy. Rev. E 56 (1991) 3310. [5] D.K.Kim, Nanoparticles: engineering, assembly, and biomedical applications, Ph.D. Thesis, MATCHEM, MET, KTH, 2002. [6] R. Hiergeist, W. Andra¨, N. Buske, R. Hergt, I. Hilger, U. Richter, W. Kaiser, J. Magn. Magn. Mater. 201 (1999) 420. [7] Z.G.M. Lacava, R.B. Azevedo, E.V. Martins, L.M. Lacava, J. Magn. Magn. Mater. 201 (1999) 431. [8] S.I. Park, J.H. Lim, J.H. Kim, J.S. Roh, C.G. Kim, C.O. Kim, Phys. Stat. Sol. (b) 241 (2004) 1662. [9] D.K. Kim, Y. Zhang, J. Magn. Magn. Mater. 225 (2001) 30. [10] D.H. Han, J.P. Wang, H.L. Luo, J. Magn. Magn. Mater. 136 (1994) 176. [11] J.M.D. Coey, Phys. Rev. Lett. 27 (1971) 1140.