- Email: [email protected]
Synthesis of ferrofluid with magnetic nanoparticles by sonochemical method for MRI contrast agent
ARTICLE IN PRESS
Journal of Magnetism and Magnetic Materials 289 (2005) 328–330 www.elsevier.com/locate/jmmm
Synthesis of ferrofluid with magnetic nanoparticles by sonochemical method for MRI contrast agent Eun Hee Kima, Hyo Sook Leea,, Byung Kook Kwakb, Byung-Kee Kimc a
Korea Institute of Geoscience & Mineral Resources, Daejeon, Republic of Korea b College of Medicine, Chung-Ang University, Seoul, Republic of Korea c Korea Institute of Machinery & Materials, Gyeongnam, Republic of Korea Available online 30 November 2004
Abstract Superparamagnetic iron oxide nanoparticles (SPIO) having high magnetization (83 emu/g) and crystallinity were synthesized by using a sonochemical method. Ferrofluids from these nanoparticles coated with oleic acid as a surfactant were prepared for magnetic resonance imaging (MRI) contrast agent. The coated SPIO could be easily dispersed in chitosan, and the hydrodynamic diameter of the coated SPIO in the chitosan solution was estimated to be 65 nm. The ferrofluids of various concentrations did not agglomerate for 30 days, indicating their good stability. The T1- and T2weighted MR images of these ferrofluids were obtained and the MRI image contrasts were similar to those of Resovists. r 2004 Elsevier B.V. All rights reserved. Keywords: Ferrite nanoparticles; Sonochemical method; Oleic acid; Chitosan; Ferrofluid; MRI contrast agent
1. Introduction Superparamagnetic iron oxide nanoparticles (SPIO) are of great interest for several clinical applications: they were recently introduced as a suitable material for drugtargeting [1], hyperthermia [2], embolotherapy [3], and magnetic resonance imaging agent [4,5]. Especially for magnetic resonance imaging (MRI) contrast agents, the SPIO as well as gadolinium or manganese salts are by far the most common. Superparamagnetic contrast agents have an advantage of producing an enhanced proton relaxation in MRI in comparison with paramagnetic ones. Consequently, less amount of SPIO agent was needed to dose into the human body than paramagnetic. To apply the magnetic fluids to MRI
Corresponding author. Fax: +82 42 868 3603.
E-mail address: [email protected] (Hyo Sook Lee).
contrast agent, the SPIO should be dispersed in a biocompatible and biodegradable carrier. In this study, we synthesized SPIO by a sonochemical method and compared with those by a coprecipitation. From the SPIO by the sonochemical method, we synthesized ferrofluids for MRI contrast agent by coating them with oleic acid as a surfactant and then dispersed them in the chitosan, which is a suitable carrier for bioapplications. We have characterized the nanoparticles by using an X-ray diffraction (XRD), a superconducting quantum interference device (SQUID), and a transmission electron microscope (TEM). The coated particles were analyzed by photon correlation spectroscopy (PCS) to measure the particle size. The MR images of the ferrofluids were obtained and compared with the images of Resovists. Resovists is a commercially available contrast agent for MRI from Schering and consists of SPIO nanoparticles coated with carboxydextrane.
0304-8853/$ - see front matter r 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.jmmm.2004.11.093
ARTICLE IN PRESS E. Hee Kim et al. / Journal of Magnetism and Magnetic Materials 289 (2005) 328–330
2. Experimental
329
311
220 200
3. Results and discussion The result of XRD showed that the ferrite nanoparticles obtained by the sonochemical and coprecipitation method had spinel magnetite crystal structure (Fig. 1). The magnetite nanoparticles by the sonochemical method showed, however, higher crystallinity than the particles by the coprecipitation. The magnetite by the sonochemical method was spherical and had the average diameter of about 15 nm as shown in Fig. 2. Considering their size, shape and crystallinity, the SPIO by sonochemistry were suitable to synthesize ferrofluids for MRI contrast agents. The superparamagnetic relaxation is an essential requirement for the SPIO nanoparticles to be used for
180 160 140
Intensity
All the chemicals were of reagent grade used without further purification. Ferric chloride hexahydrate ferrous chloride tetrahydrate (FeCl3 6H2O), (FeCl2 4H2O), and oleic acid (C18H34O2) were purchased from Aldrich, while ammonium hydroxide (NH4OH) and sodium hydroxide (NaOH) from Junsei. A mixed solution of 0.15 M FeCl2 (50 ml, 7.5 mM) and 0.30 M FeCl3 (50 ml, 15.0 mM) was prepared. As soon as ultrasonic waves were irradiated (ULSSO HITECH Co. LTD, Model ULH700S, 10 mm, Ti horn, 20 kHz) to the mixture at 665 W, we rapidly added NH4OH (60.0 mM) solution to the mixture to result in black nanoparticles at room temperature. These black nanoparticles were washed free of anions with deionized water, and the particle size and morphology were examined with TEM (Philips-F20). The wet particles were dried at 80 1C in a vacuum oven to characterize the crystal structure and magnetic properties by using an XRD (Rigaku D/Max II) and a SQUID (Quantum design-MPMS5). The properties of the synthetized SPIO by the sonochemical method were compared with those of the SPIO by the coprecipitaion method. Washed iron ferrite nanoparticles (1.73 g) were decanted and coated with 0.87 ml of oleic acid at 70 1C for 30 min. To prepare ferrofluids, the coated SPIO nanoparticles were dispersed in 112.5 ml of chitosan by ultrasonic irradiation for 30 min. The synthesized ferrofluids were purified by a centrifuge at 3000 rpm for 20 min at room temperature. The hydrodynamic diameters of the coated ferrite nanoparticles were calculated by PCS (MASTERSIZER 2000). The T1- and T2weighted MR images of these ferrofluids were obtained. All MR imaging examinations were performed with a 1.0 T imaging system (Medius Co. Korea, Model Magnum 1.0 T) by using a spin echo technique. The MR images of the ferrofluids were compared to those of Resovists.
440
220
120
111
100
400
511 533
(b)
80 60 40 20
(a)
0 -20 0
20
40
60
80
100
Angle
Fig. 1. X-ray diffraction pattern (Cu=Ka radiation) of magnetite nanoparticles by (a) co-precipitation method and (b) sonochemical method.
Fig. 2. TEM images of magnetite nanoparticles by the sonochemical method.
MRI contrast enhancement. The magnetic hysteresis curves of magnetite nanoparticles by the sonochemical and coprecipitation are shown in Fig. 3. The hysteresis curves of these nanoparticles had no coercive force, all magnetite nanoparticles from two different methods behaved superparamagnetic. The saturation magnetization of magnetite particles by the sonochemical (83 emu/ g) was higher than that of nanoparticles by coprecipitation (51 emu/g). The mean particle size of the coated SPIO nanoparticles was measured to be 65 nm by using PCS, which was close to that of the SPIO (61 nm) in Resovists. Resovists would be injected to an adult to result in the Fe concentration of 0.2 mM in the liver. To cover the Fe concentration of Resovists, we first prepared the
ARTICLE IN PRESS E. Hee Kim et al. / Journal of Magnetism and Magnetic Materials 289 (2005) 328–330
330 100
Magnetization (emu/g)
80 60 40
A
20
sonochemical method
0
B
A
B
co-precipitation method −20 −40 −60 −80
H 2O
−100 -60000
-40000
-20000
0
20000
40000
60000
Magnetic Field (Oe)
Fig. 3. Magnetic hysteresis curves of the SPIO nanoparticles by the sonochemical and coprecipitation method.
ferrofluids with Fe concentration of 0.2 M, and then diluted the ferrofluid with varying Fe concentration from 0.02 mM to 0.2 M with 5% dextrose solution. These ferrofluid of various concentrations were stable for 30 days without precipitation. We obtained both T1and T2-weighted images of Resovists and the ferrofluids prepared with the same concentration as Resovists. The images of pure water were also taken as standard MR images (Fig. 4). The T1-weighted images of Resovists and the ferrofluids were brighter than that of the water while T2-weighted images darker. Both the T1- and T2-weighted images of the ferrofluids were similar to those of Resovists.
4. Conclusions Superparamagnetic iron oxide nanoparticles (SPIO) were synthesized by the sonochemical method. These spherical particles of about 15 nm in diameter showed superparamagnetic behavior. We
Fig. 4. T1- (left) and T2-weighted image (right) of Resovists (A), synthetic ferrofluid (B) and water (H2O) in the same Fe concentration of 0.2 mM.
confirmed these SPIO could be well dispersed in chitosan to make ferrofluids. And the ferrofluids exhibited the enhancement of MRI contrasts comparable to Resovists in vitro. We are carrying out experimentation in vivo. Still much work remains to be done to make the ferrofluids reliable for the clinical applications.
References [1] A.S. Lu¨bbe, C. Bergemann, W. Huhnt, T. Fricke, H. Reiss, J.W. Brock, D. Huhn, Cancer Res. 56 (1996) 4694. [2] A. Jordan, R. Scholz, P. Wust, H. Fa¨hling, R. Felix, J. Magn. Magn. Mater. 201 (1999) 413. [3] J. Liu, G.A. Flores, R. Sheng, J. Magn. Magn. Mater. 225 (2001) 209. [4] L. Babes, B. Denizot, G. Tanguy, J.J.L. Jeune, P. Jallet, J. Colloid Interface Sci. 212 (1999) 474. [5] D.K. Kim, Y. Zhang, J. Kehr, T. Klason, B. Bjelke, M. Muhammed, J. Magn. Magn. Mater. 225 (2001) 256.
Journal of Magnetism and Magnetic Materials 289 (2005) 328–330 www.elsevier.com/locate/jmmm
Synthesis of ferrofluid with magnetic nanoparticles by sonochemical method for MRI contrast agent Eun Hee Kima, Hyo Sook Leea,, Byung Kook Kwakb, Byung-Kee Kimc a
Korea Institute of Geoscience & Mineral Resources, Daejeon, Republic of Korea b College of Medicine, Chung-Ang University, Seoul, Republic of Korea c Korea Institute of Machinery & Materials, Gyeongnam, Republic of Korea Available online 30 November 2004
Abstract Superparamagnetic iron oxide nanoparticles (SPIO) having high magnetization (83 emu/g) and crystallinity were synthesized by using a sonochemical method. Ferrofluids from these nanoparticles coated with oleic acid as a surfactant were prepared for magnetic resonance imaging (MRI) contrast agent. The coated SPIO could be easily dispersed in chitosan, and the hydrodynamic diameter of the coated SPIO in the chitosan solution was estimated to be 65 nm. The ferrofluids of various concentrations did not agglomerate for 30 days, indicating their good stability. The T1- and T2weighted MR images of these ferrofluids were obtained and the MRI image contrasts were similar to those of Resovists. r 2004 Elsevier B.V. All rights reserved. Keywords: Ferrite nanoparticles; Sonochemical method; Oleic acid; Chitosan; Ferrofluid; MRI contrast agent
1. Introduction Superparamagnetic iron oxide nanoparticles (SPIO) are of great interest for several clinical applications: they were recently introduced as a suitable material for drugtargeting [1], hyperthermia [2], embolotherapy [3], and magnetic resonance imaging agent [4,5]. Especially for magnetic resonance imaging (MRI) contrast agents, the SPIO as well as gadolinium or manganese salts are by far the most common. Superparamagnetic contrast agents have an advantage of producing an enhanced proton relaxation in MRI in comparison with paramagnetic ones. Consequently, less amount of SPIO agent was needed to dose into the human body than paramagnetic. To apply the magnetic fluids to MRI
Corresponding author. Fax: +82 42 868 3603.
E-mail address: [email protected] (Hyo Sook Lee).
contrast agent, the SPIO should be dispersed in a biocompatible and biodegradable carrier. In this study, we synthesized SPIO by a sonochemical method and compared with those by a coprecipitation. From the SPIO by the sonochemical method, we synthesized ferrofluids for MRI contrast agent by coating them with oleic acid as a surfactant and then dispersed them in the chitosan, which is a suitable carrier for bioapplications. We have characterized the nanoparticles by using an X-ray diffraction (XRD), a superconducting quantum interference device (SQUID), and a transmission electron microscope (TEM). The coated particles were analyzed by photon correlation spectroscopy (PCS) to measure the particle size. The MR images of the ferrofluids were obtained and compared with the images of Resovists. Resovists is a commercially available contrast agent for MRI from Schering and consists of SPIO nanoparticles coated with carboxydextrane.
0304-8853/$ - see front matter r 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.jmmm.2004.11.093
ARTICLE IN PRESS E. Hee Kim et al. / Journal of Magnetism and Magnetic Materials 289 (2005) 328–330
2. Experimental
329
311
220 200
3. Results and discussion The result of XRD showed that the ferrite nanoparticles obtained by the sonochemical and coprecipitation method had spinel magnetite crystal structure (Fig. 1). The magnetite nanoparticles by the sonochemical method showed, however, higher crystallinity than the particles by the coprecipitation. The magnetite by the sonochemical method was spherical and had the average diameter of about 15 nm as shown in Fig. 2. Considering their size, shape and crystallinity, the SPIO by sonochemistry were suitable to synthesize ferrofluids for MRI contrast agents. The superparamagnetic relaxation is an essential requirement for the SPIO nanoparticles to be used for
180 160 140
Intensity
All the chemicals were of reagent grade used without further purification. Ferric chloride hexahydrate ferrous chloride tetrahydrate (FeCl3 6H2O), (FeCl2 4H2O), and oleic acid (C18H34O2) were purchased from Aldrich, while ammonium hydroxide (NH4OH) and sodium hydroxide (NaOH) from Junsei. A mixed solution of 0.15 M FeCl2 (50 ml, 7.5 mM) and 0.30 M FeCl3 (50 ml, 15.0 mM) was prepared. As soon as ultrasonic waves were irradiated (ULSSO HITECH Co. LTD, Model ULH700S, 10 mm, Ti horn, 20 kHz) to the mixture at 665 W, we rapidly added NH4OH (60.0 mM) solution to the mixture to result in black nanoparticles at room temperature. These black nanoparticles were washed free of anions with deionized water, and the particle size and morphology were examined with TEM (Philips-F20). The wet particles were dried at 80 1C in a vacuum oven to characterize the crystal structure and magnetic properties by using an XRD (Rigaku D/Max II) and a SQUID (Quantum design-MPMS5). The properties of the synthetized SPIO by the sonochemical method were compared with those of the SPIO by the coprecipitaion method. Washed iron ferrite nanoparticles (1.73 g) were decanted and coated with 0.87 ml of oleic acid at 70 1C for 30 min. To prepare ferrofluids, the coated SPIO nanoparticles were dispersed in 112.5 ml of chitosan by ultrasonic irradiation for 30 min. The synthesized ferrofluids were purified by a centrifuge at 3000 rpm for 20 min at room temperature. The hydrodynamic diameters of the coated ferrite nanoparticles were calculated by PCS (MASTERSIZER 2000). The T1- and T2weighted MR images of these ferrofluids were obtained. All MR imaging examinations were performed with a 1.0 T imaging system (Medius Co. Korea, Model Magnum 1.0 T) by using a spin echo technique. The MR images of the ferrofluids were compared to those of Resovists.
440
220
120
111
100
400
511 533
(b)
80 60 40 20
(a)
0 -20 0
20
40
60
80
100
Angle
Fig. 1. X-ray diffraction pattern (Cu=Ka radiation) of magnetite nanoparticles by (a) co-precipitation method and (b) sonochemical method.
Fig. 2. TEM images of magnetite nanoparticles by the sonochemical method.
MRI contrast enhancement. The magnetic hysteresis curves of magnetite nanoparticles by the sonochemical and coprecipitation are shown in Fig. 3. The hysteresis curves of these nanoparticles had no coercive force, all magnetite nanoparticles from two different methods behaved superparamagnetic. The saturation magnetization of magnetite particles by the sonochemical (83 emu/ g) was higher than that of nanoparticles by coprecipitation (51 emu/g). The mean particle size of the coated SPIO nanoparticles was measured to be 65 nm by using PCS, which was close to that of the SPIO (61 nm) in Resovists. Resovists would be injected to an adult to result in the Fe concentration of 0.2 mM in the liver. To cover the Fe concentration of Resovists, we first prepared the
ARTICLE IN PRESS E. Hee Kim et al. / Journal of Magnetism and Magnetic Materials 289 (2005) 328–330
330 100
Magnetization (emu/g)
80 60 40
A
20
sonochemical method
0
B
A
B
co-precipitation method −20 −40 −60 −80
H 2O
−100 -60000
-40000
-20000
0
20000
40000
60000
Magnetic Field (Oe)
Fig. 3. Magnetic hysteresis curves of the SPIO nanoparticles by the sonochemical and coprecipitation method.
ferrofluids with Fe concentration of 0.2 M, and then diluted the ferrofluid with varying Fe concentration from 0.02 mM to 0.2 M with 5% dextrose solution. These ferrofluid of various concentrations were stable for 30 days without precipitation. We obtained both T1and T2-weighted images of Resovists and the ferrofluids prepared with the same concentration as Resovists. The images of pure water were also taken as standard MR images (Fig. 4). The T1-weighted images of Resovists and the ferrofluids were brighter than that of the water while T2-weighted images darker. Both the T1- and T2-weighted images of the ferrofluids were similar to those of Resovists.
4. Conclusions Superparamagnetic iron oxide nanoparticles (SPIO) were synthesized by the sonochemical method. These spherical particles of about 15 nm in diameter showed superparamagnetic behavior. We
Fig. 4. T1- (left) and T2-weighted image (right) of Resovists (A), synthetic ferrofluid (B) and water (H2O) in the same Fe concentration of 0.2 mM.
confirmed these SPIO could be well dispersed in chitosan to make ferrofluids. And the ferrofluids exhibited the enhancement of MRI contrasts comparable to Resovists in vitro. We are carrying out experimentation in vivo. Still much work remains to be done to make the ferrofluids reliable for the clinical applications.
References [1] A.S. Lu¨bbe, C. Bergemann, W. Huhnt, T. Fricke, H. Reiss, J.W. Brock, D. Huhn, Cancer Res. 56 (1996) 4694. [2] A. Jordan, R. Scholz, P. Wust, H. Fa¨hling, R. Felix, J. Magn. Magn. Mater. 201 (1999) 413. [3] J. Liu, G.A. Flores, R. Sheng, J. Magn. Magn. Mater. 225 (2001) 209. [4] L. Babes, B. Denizot, G. Tanguy, J.J.L. Jeune, P. Jallet, J. Colloid Interface Sci. 212 (1999) 474. [5] D.K. Kim, Y. Zhang, J. Kehr, T. Klason, B. Bjelke, M. Muhammed, J. Magn. Magn. Mater. 225 (2001) 256.