- Email: [email protected]
Surface modification of magnetite nanoparticles for biomedical applications
ARTICLE IN PRESS Journal of Magnetism and Magnetic Materials 321 (2009) 1397–1399
Contents lists available at ScienceDirect
Journal of Magnetism and Magnetic Materials journal homepage: www.elsevier.com/locate/jmmm
Surface modification of magnetite nanoparticles for biomedical applications Carola Barrera, Adriana Herrera, Yashira Zayas, Carlos Rinaldi ¨ ez Campus, Puerto Rico Institute for Functional Nanomaterials, PO Box 9046, Mayagu ¨ ez, PR 00680, USA Department of Chemical Engineering, University of Puerto Rico-Mayagu
a r t i c l e in fo
abstract
Available online 20 February 2009
The preparation of magnetite nanoparticles with narrow size distributions using poly(ethylene glycol) (PEG–COOH) or carboxymethyl dextran (CMDx) chains covalently attached to the particle surface using carbodiimide chemistry is described. Particles were synthesized by thermal decomposition and modified with 3-aminopropyl trimethoxysilane (APS) to render particles with reactive amine groups (–NH2) on their surface. Amines were then reacted with carboxyl groups in PEG–COOH or CMDx using carbodiimide chemistry in water. The size and stability of the functionalized magnetic nanoparticles was studied as a function of pH and ionic strength using dynamic light scattering and zeta potential measurements. & 2009 Elsevier B.V. All rights reserved.
Keywords: Magnetite Thermal decomposition Carbodiimide PEG Dextran
Control of particle size distribution and innovative functionalization techniques are critical steps needed to effectively implement the use of magnetic nanoparticles in medical applications [1–6]. Techniques such as thermal decomposition offer an alternative to the commonly used co-precipitation method to produce magnetic nanoparticles with a narrow size distribution and hence uniform magnetic properties. This is achieved by decomposition of metallic precursors in high-boiling-point solvents using oleic acid (OA) as surfactant [7]. To obtain stable suspensions of these particles in water, OA on the surface of the particles is exchanged for a hydrophilic molecule that not only stabilizes the particle in suspension but can also covalently attach to the surface of the particle, avoiding subsequent desorption and particle precipitation. Organo-functional silanes, such as 3-aminopropyl trimethoxysilane (APS), offer an alternative to chemically bond molecules to iron oxide surfaces leaving reactive amine end groups (–NH2). This group can be further reacted to link other molecules with functional carboxyl groups (–COOH) by amide reactions. The formation of amides using carbodiimides is a technique commonly used in peptide synthesis where carboxylic acids are activated using molecules like 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) to form an oacylisourea intermediate that is stabilized using N-hydroxysuccinimide (NHS) and that reacts with amines to form a peptide bond [8]. This technique offers a route to obtain singly dispersed magnetite nanoparticle modified with covalently grafted carboxymethyl dextran (CMDx) and poly(ethylene glycol) (PEG) without resulting in encapsulation of particle clusters in polymer matrixes
Corresponding author. Tel.: +1787 832 4040x3585; fax: +1787 265 3818.
E-mail address: [email protected] (C. Rinaldi). 0304-8853/$ - see front matter & 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jmmm.2009.02.046
or using crosslinkers to avoid eventual desorption of the polymers from the particle surface. Magnetite nanoparticles (Fe3O4) with narrow size distributions were synthesized by the thermal decomposition method using 1-octadecene at 320 1C. Afterwards, these nanoparticles were washed with ethanol, centrifuged at 7500 rpm for 15 min, and then suspended in 80 ml of hexane at 45% v/v, obtaining a stable ferrofluid. Magnetite nanoparticles coated with OA were functionalized with APS via ligand exchange obtaining –NH2 end groups on the nanoparticle surface. In this procedure, 6 ml of APS and 50 mL of acetic acid were added to the colloidal suspension of magnetite–OA nanoparticles and mechanically stirred at room temperature for three days, allowing the precipitation of the functionalized magnetic-APS nanoparticles from the hexane solution. Removal of free OA and APS molecules was carried out by washing the magnetite–APS nanoparticles three times with 50 ml of hexane, followed by magnetic decantation. Finally, these functionalized magnetite–APS nanoparticles were washed one time with 50 ml of ethanol and then dried at room temperature. To obtain PEG- or dextran-modified magnetite nanoparticles, particles were suspended in deionized water at pH 4.5 to obtain a 10 mg/ml solution. PEG–COOH was obtained by oxidation of terminal hydroxyl groups of mono-methoxy PEG with a molecular weight of 2 kDa using Jone’s reagent [9]. A commercial CMDx with a molecular weight of 10–20 kDa and 18 COOH groups per gram was used. A solution was prepared where PEG–COOH or CMDx was dissolved in deionized water at a concentration of 100 mg/ml. To this solution, EDC and NHS were added in equimolar proportions with respect to PEG–COOH or CMDx and mixed for 30 min to activate carboxyl groups at a pH of 4.5. Both solutions were mixed and left in a shaker for 24 h at room temperature. In the case of magnetite–CMDx nanoparticles, ethanol was added to the suspension after reaction, followed by centrifugation at
ARTICLE IN PRESS C. Barrera et al. / Journal of Magnetism and Magnetic Materials 321 (2009) 1397–1399
4000
3500
2500
2000
1500
1086 1004 924 1007
1637 1567 1633 1589 3000
1091
1633 1557
2968 2897
3391
3154
1557 cm 1 characteristic of the amine groups (–NH2) on the surface of the particles. Bands at 1086, 1004, and 924 cm 1 correspond to the condensation of siloxane molecules on the surface of the particle. Successful functionalization with PEG and CMDx was confirmed in spectrum (b) and (c) by the appearance of bands at 1007 and 1091 cm 1, characteristic of the –COC vibration in PEG and CMDx, respectively. The appearance of bands at about 3300 and 1580 cm 1, characteristic of the –C(QO)–N–H vibration, confirmed the amide bond formed between amine groups on the surface of the particle and carboxyl groups in PEG or CMDx [12]. Particle stability was studied using zeta potential as a function of pH by suspending the particles in water with 0.1 M KNO3 and using 2 M KOH and HNO3 to adjust pH from 2 to 11. As seen in Fig. 3(i), the surface of particles coated with APS has a positive charge over almost the entire pH range due to the presence of –NH3+ groups with an isoelectric point (pI) at a pH of about 10.5, above which particles precipitate. After modification with CMDx,
3330
7500 rpm for 15 min. PEG-modified magnetite nanoparticles were dried in a vacuum oven at 60 1C, suspended in acetone, and precipitated with ether to remove unreacted PEG. Particle size and size distribution were studied using a JEOL 1200EX transmission electron microscope (TEM) and a Brookhaven Instrument BI-90 Plus particle size analyzer. Stability in water at physiological conditions was studied using zeta potential as a function of pH and ionic strength. The amide bond between amine groups on the surface of the particle and carboxyl groups in each of the polymers was confirmed by infrared spectroscopy (FT-IR) using a Varian 800. Particle core size was analyzed using samples deposited on copper grids by TEM. Fig. 1 (a) shows magnetite nanoparticles obtained with a narrow size distribution and number mean diameter Dpg of 13 nm and a geometric deviation ln(sg) of 0.08 after analyzing 100 particles using Image J and fitting using a lognormal distribution. No particle agglomeration or change in size, as determined from similar statistical analysis, was observed after ligand exchange with APS or during grafting of PEG–COOH or CMDx. DLS measurements of particles initially coated with OA show a particle number mean hydrodynamic size of 19 nm after suspension in hexane and filtering using a 0.22 mm PTFE filter. This size is in good agreement with TEM and values reported for the chain length of OA of about 2–3 nm [10]. After ligand exchange with APS, the hydrodynamic size of the particles was 19 nm when suspended in deionized water at pH 4.5 and filtered using a 0.22 mm nylon filter. This size corresponds to a monolayer of APS molecules on the surface of the particles, assuming the length of an APS chain is about 2 nm [11]. For CMDx-coated nanoparticles, the hydrodynamic size increased to 31 nm which suggests that more than one carboxyl group in the same CMDx chain attaches to each particle. This resulted in singly dispersed particles coated with CMDx as shown in Fig. 1 micrograph (d). A size of 43 nm was obtained for PEG-coated nanoparticles, close to an expected diameter of about 42 nm estimated using a PEG chain length of about 13 nm, calculated for a molecular weight of 2 kDa using Gauss View 3.07. Infrared spectroscopy of magnetite–APS nanoparticles shown in spectrum (a) of Fig. 2 reveals relevant bands at 3154, 1633, and
A.U
1398
1000
-1
wavenumber (cm ) Fig. 2. Infrared spectrums of (a) magnetic-APS nanoparticles, (b) magnetic-PEG nanoparticles, and (c) magnetic-CMDx nanoparticles
Fig. 1. Magnetite nanoparticles synthesized by thermal decomposition using (a) OA as surfactant, (b) after ligand exchange with APS, (c) modified with PEG–COOH, and (d) modified with CMDx
ARTICLE IN PRESS C. Barrera et al. / Journal of Magnetism and Magnetic Materials 321 (2009) 1397–1399
Fig. 3. (i) Zeta potential and (ii) particle size as a function of pH for (a) magnetite–APS nanoparticles, (b) magnetite–PEG nanoparticles, and (c) magnetite–CMDx nanoparticles.
Zeta Potential (mV)
40
20
ticles. The particle size was also monitored as a function of pH with no considerable variations as shown in Fig. 3(ii), demonstrating that particles are stabilized by both electrostatic and steric repulsion between polymer chains on the surface of the particles. Similar experiments were performed as a function of ionic strength by measuring zeta potential as a function of NaCl concentration from 0.019 to 0.14 M at pH 7 for CMDx and PEG–COOH-coated magnetite nanoparticles. Fig. 4 shows a decrease in zeta potential in both cases as salt concentration increased in accordance with the Debye–Hu¨ckel theory [14]. No particle precipitation was observed for this range of salt concentration. The equilibrium magnetization of the functionalized magnetite nanoparticles was analyzed in a DC magnetic field using a Quantum Design MPMS-XL7 SQUID magnetometer. Both types of particles suspended in deionized water at pH 7 had superparamagnetic behavior (not shown). From the magnetic measurements we estimated a magnetic core size of about 7 nm with a geometric deviation of 0.22 for magnetite–APS nanoparticles suspended in aqueous media [15]. The calculated magnetic size is considerably smaller than that observed from TEM measurements and could be the result of the formation of a so-called ‘‘magnetically dead’’ layer on the particle surface, due to Fe atoms linked to APS molecules through Si–O bonds and which do not contribute to the magnetic moment of the particle. We have successfully obtained magnetic nanoparticles with a narrow size distribution and coated with PEG and CMDx covalently grafted to the surface of the particles using carbodiimide chemistry. No agglomeration of the particles was observed during the functionalization steps as confirmed by TEM and DLS. Furthermore, zeta potential measurements show that the magnetic nanoparticles coated with PEG or CMDx are highly stable in water at pH 7 and in the presence of electrolytes such as NaCl, which makes these modified magnetic nanoparticles attractive for biological applications such as magnetic fluid hyperthermia for cancer treatment or as MRI contrast agents. This work was supported by the US National Science Foundation (Grants CBET-0329374, DMR-0351449, and OIA-0701525), NASA (NCC5-595). We are grateful to the Integrated Advanced Microscopy facility at the Cornell Center for Materials Research (CCMR) supported by the NSF–MRSEC program (NSF DMR-0520404) and Prof. Juan Hinestroza and Alejandra Andere for performing TEM measurements.
0
-20
-40
1399
References
0.00 0.02 0.04
0.06 0.08 0.10 0.12 0.14 0.16
[NaCl] Fig. 4. Zeta potential for (a) magnetite–PEG and (b) magnetite–CMDx nanoparticles as a function of NaCl concentration in water at pH 7.
the surface charge changed to negative due to the presence of unreacted carboxyl groups remaining in CMDx grafted to the particle. In this case, the observed pI shifted to 2.5 with no particle precipitation over the entire pH range. For particles coated with PEG–COOH, the particle surface charge switches from a positive charge at pH below 7 to negative at pH above 7. In this case, the surface charge is attributed to ions adsorbed from solution to the PEG layer on the particle surface [13]. No precipitation was observed over the entire pH range for the PEG-coated nanopar-
[1] Q.A. Pankhurst, J. Connolly, S.K. Jones, J. Dobson, J. Phys. D: Appl. Phys. 36 (2003) R167. [2] C.C. Berry, A.S.G. Curtis, J. Phys. D: Appl. Phys. 36 (2003) R198. [3] C.C. Berry, The Royal Society of Chemistry 15 (2005) 543. [4] S. Mornet, J. Portier, E. Duguet, J. Magn. Magn. Mater. 293 (2005) 127. [5] E. Parton, R.d. Palma, G. Borghs, Nanotechnology (2007) 47. [6] A.P. Herrera, C. Barrera, C. Rinaldi, J. Mater. Chem. 18 (2008) 3650. [7] J. Park, K. An, Y. Hwang, et al., Nature 3 (2004) 891. [8] N. Nakajima, Y. Ikada, Bioconjugate Chem. 6 (1994) 123. [9] B.S. Lele, M.G. Kulkarni, J. Appl. Polym. Sci. 70 (1998) 883. [10] L. Zhang, R. He, H. Gu, Appl. Surf. Sci. 253 (2006) 2611. [11] K. Bierbaum, M. Kinzler, C. Woll, M. Grunze, Langmuir 11 (1995) 512. [12] D. Lin-Vien, N. Colthup, W. Fateley, J. Graselli, The Handbook of Infrared and Raman Characteristic Frequencies of Organic Molecules, Academic Press, San Diego, 1991. [13] R.d. Palma, S. Peeters, J.M.V. Bael, et al., Chem. Mater. 19 (2007) 1821. [14] P.C. Hiemenz, R. Rajagopalan, Principles of colloid and surface chemistry. Marcel Dekker, New York. [15] R. Chantrell, J. Popplewell, S. Charles, IEEE Trans. Magn. 14 (1978) 975.
Contents lists available at ScienceDirect
Journal of Magnetism and Magnetic Materials journal homepage: www.elsevier.com/locate/jmmm
Surface modification of magnetite nanoparticles for biomedical applications Carola Barrera, Adriana Herrera, Yashira Zayas, Carlos Rinaldi ¨ ez Campus, Puerto Rico Institute for Functional Nanomaterials, PO Box 9046, Mayagu ¨ ez, PR 00680, USA Department of Chemical Engineering, University of Puerto Rico-Mayagu
a r t i c l e in fo
abstract
Available online 20 February 2009
The preparation of magnetite nanoparticles with narrow size distributions using poly(ethylene glycol) (PEG–COOH) or carboxymethyl dextran (CMDx) chains covalently attached to the particle surface using carbodiimide chemistry is described. Particles were synthesized by thermal decomposition and modified with 3-aminopropyl trimethoxysilane (APS) to render particles with reactive amine groups (–NH2) on their surface. Amines were then reacted with carboxyl groups in PEG–COOH or CMDx using carbodiimide chemistry in water. The size and stability of the functionalized magnetic nanoparticles was studied as a function of pH and ionic strength using dynamic light scattering and zeta potential measurements. & 2009 Elsevier B.V. All rights reserved.
Keywords: Magnetite Thermal decomposition Carbodiimide PEG Dextran
Control of particle size distribution and innovative functionalization techniques are critical steps needed to effectively implement the use of magnetic nanoparticles in medical applications [1–6]. Techniques such as thermal decomposition offer an alternative to the commonly used co-precipitation method to produce magnetic nanoparticles with a narrow size distribution and hence uniform magnetic properties. This is achieved by decomposition of metallic precursors in high-boiling-point solvents using oleic acid (OA) as surfactant [7]. To obtain stable suspensions of these particles in water, OA on the surface of the particles is exchanged for a hydrophilic molecule that not only stabilizes the particle in suspension but can also covalently attach to the surface of the particle, avoiding subsequent desorption and particle precipitation. Organo-functional silanes, such as 3-aminopropyl trimethoxysilane (APS), offer an alternative to chemically bond molecules to iron oxide surfaces leaving reactive amine end groups (–NH2). This group can be further reacted to link other molecules with functional carboxyl groups (–COOH) by amide reactions. The formation of amides using carbodiimides is a technique commonly used in peptide synthesis where carboxylic acids are activated using molecules like 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) to form an oacylisourea intermediate that is stabilized using N-hydroxysuccinimide (NHS) and that reacts with amines to form a peptide bond [8]. This technique offers a route to obtain singly dispersed magnetite nanoparticle modified with covalently grafted carboxymethyl dextran (CMDx) and poly(ethylene glycol) (PEG) without resulting in encapsulation of particle clusters in polymer matrixes
Corresponding author. Tel.: +1787 832 4040x3585; fax: +1787 265 3818.
E-mail address: [email protected] (C. Rinaldi). 0304-8853/$ - see front matter & 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jmmm.2009.02.046
or using crosslinkers to avoid eventual desorption of the polymers from the particle surface. Magnetite nanoparticles (Fe3O4) with narrow size distributions were synthesized by the thermal decomposition method using 1-octadecene at 320 1C. Afterwards, these nanoparticles were washed with ethanol, centrifuged at 7500 rpm for 15 min, and then suspended in 80 ml of hexane at 45% v/v, obtaining a stable ferrofluid. Magnetite nanoparticles coated with OA were functionalized with APS via ligand exchange obtaining –NH2 end groups on the nanoparticle surface. In this procedure, 6 ml of APS and 50 mL of acetic acid were added to the colloidal suspension of magnetite–OA nanoparticles and mechanically stirred at room temperature for three days, allowing the precipitation of the functionalized magnetic-APS nanoparticles from the hexane solution. Removal of free OA and APS molecules was carried out by washing the magnetite–APS nanoparticles three times with 50 ml of hexane, followed by magnetic decantation. Finally, these functionalized magnetite–APS nanoparticles were washed one time with 50 ml of ethanol and then dried at room temperature. To obtain PEG- or dextran-modified magnetite nanoparticles, particles were suspended in deionized water at pH 4.5 to obtain a 10 mg/ml solution. PEG–COOH was obtained by oxidation of terminal hydroxyl groups of mono-methoxy PEG with a molecular weight of 2 kDa using Jone’s reagent [9]. A commercial CMDx with a molecular weight of 10–20 kDa and 18 COOH groups per gram was used. A solution was prepared where PEG–COOH or CMDx was dissolved in deionized water at a concentration of 100 mg/ml. To this solution, EDC and NHS were added in equimolar proportions with respect to PEG–COOH or CMDx and mixed for 30 min to activate carboxyl groups at a pH of 4.5. Both solutions were mixed and left in a shaker for 24 h at room temperature. In the case of magnetite–CMDx nanoparticles, ethanol was added to the suspension after reaction, followed by centrifugation at
ARTICLE IN PRESS C. Barrera et al. / Journal of Magnetism and Magnetic Materials 321 (2009) 1397–1399
4000
3500
2500
2000
1500
1086 1004 924 1007
1637 1567 1633 1589 3000
1091
1633 1557
2968 2897
3391
3154
1557 cm 1 characteristic of the amine groups (–NH2) on the surface of the particles. Bands at 1086, 1004, and 924 cm 1 correspond to the condensation of siloxane molecules on the surface of the particle. Successful functionalization with PEG and CMDx was confirmed in spectrum (b) and (c) by the appearance of bands at 1007 and 1091 cm 1, characteristic of the –COC vibration in PEG and CMDx, respectively. The appearance of bands at about 3300 and 1580 cm 1, characteristic of the –C(QO)–N–H vibration, confirmed the amide bond formed between amine groups on the surface of the particle and carboxyl groups in PEG or CMDx [12]. Particle stability was studied using zeta potential as a function of pH by suspending the particles in water with 0.1 M KNO3 and using 2 M KOH and HNO3 to adjust pH from 2 to 11. As seen in Fig. 3(i), the surface of particles coated with APS has a positive charge over almost the entire pH range due to the presence of –NH3+ groups with an isoelectric point (pI) at a pH of about 10.5, above which particles precipitate. After modification with CMDx,
3330
7500 rpm for 15 min. PEG-modified magnetite nanoparticles were dried in a vacuum oven at 60 1C, suspended in acetone, and precipitated with ether to remove unreacted PEG. Particle size and size distribution were studied using a JEOL 1200EX transmission electron microscope (TEM) and a Brookhaven Instrument BI-90 Plus particle size analyzer. Stability in water at physiological conditions was studied using zeta potential as a function of pH and ionic strength. The amide bond between amine groups on the surface of the particle and carboxyl groups in each of the polymers was confirmed by infrared spectroscopy (FT-IR) using a Varian 800. Particle core size was analyzed using samples deposited on copper grids by TEM. Fig. 1 (a) shows magnetite nanoparticles obtained with a narrow size distribution and number mean diameter Dpg of 13 nm and a geometric deviation ln(sg) of 0.08 after analyzing 100 particles using Image J and fitting using a lognormal distribution. No particle agglomeration or change in size, as determined from similar statistical analysis, was observed after ligand exchange with APS or during grafting of PEG–COOH or CMDx. DLS measurements of particles initially coated with OA show a particle number mean hydrodynamic size of 19 nm after suspension in hexane and filtering using a 0.22 mm PTFE filter. This size is in good agreement with TEM and values reported for the chain length of OA of about 2–3 nm [10]. After ligand exchange with APS, the hydrodynamic size of the particles was 19 nm when suspended in deionized water at pH 4.5 and filtered using a 0.22 mm nylon filter. This size corresponds to a monolayer of APS molecules on the surface of the particles, assuming the length of an APS chain is about 2 nm [11]. For CMDx-coated nanoparticles, the hydrodynamic size increased to 31 nm which suggests that more than one carboxyl group in the same CMDx chain attaches to each particle. This resulted in singly dispersed particles coated with CMDx as shown in Fig. 1 micrograph (d). A size of 43 nm was obtained for PEG-coated nanoparticles, close to an expected diameter of about 42 nm estimated using a PEG chain length of about 13 nm, calculated for a molecular weight of 2 kDa using Gauss View 3.07. Infrared spectroscopy of magnetite–APS nanoparticles shown in spectrum (a) of Fig. 2 reveals relevant bands at 3154, 1633, and
A.U
1398
1000
-1
wavenumber (cm ) Fig. 2. Infrared spectrums of (a) magnetic-APS nanoparticles, (b) magnetic-PEG nanoparticles, and (c) magnetic-CMDx nanoparticles
Fig. 1. Magnetite nanoparticles synthesized by thermal decomposition using (a) OA as surfactant, (b) after ligand exchange with APS, (c) modified with PEG–COOH, and (d) modified with CMDx
ARTICLE IN PRESS C. Barrera et al. / Journal of Magnetism and Magnetic Materials 321 (2009) 1397–1399
Fig. 3. (i) Zeta potential and (ii) particle size as a function of pH for (a) magnetite–APS nanoparticles, (b) magnetite–PEG nanoparticles, and (c) magnetite–CMDx nanoparticles.
Zeta Potential (mV)
40
20
ticles. The particle size was also monitored as a function of pH with no considerable variations as shown in Fig. 3(ii), demonstrating that particles are stabilized by both electrostatic and steric repulsion between polymer chains on the surface of the particles. Similar experiments were performed as a function of ionic strength by measuring zeta potential as a function of NaCl concentration from 0.019 to 0.14 M at pH 7 for CMDx and PEG–COOH-coated magnetite nanoparticles. Fig. 4 shows a decrease in zeta potential in both cases as salt concentration increased in accordance with the Debye–Hu¨ckel theory [14]. No particle precipitation was observed for this range of salt concentration. The equilibrium magnetization of the functionalized magnetite nanoparticles was analyzed in a DC magnetic field using a Quantum Design MPMS-XL7 SQUID magnetometer. Both types of particles suspended in deionized water at pH 7 had superparamagnetic behavior (not shown). From the magnetic measurements we estimated a magnetic core size of about 7 nm with a geometric deviation of 0.22 for magnetite–APS nanoparticles suspended in aqueous media [15]. The calculated magnetic size is considerably smaller than that observed from TEM measurements and could be the result of the formation of a so-called ‘‘magnetically dead’’ layer on the particle surface, due to Fe atoms linked to APS molecules through Si–O bonds and which do not contribute to the magnetic moment of the particle. We have successfully obtained magnetic nanoparticles with a narrow size distribution and coated with PEG and CMDx covalently grafted to the surface of the particles using carbodiimide chemistry. No agglomeration of the particles was observed during the functionalization steps as confirmed by TEM and DLS. Furthermore, zeta potential measurements show that the magnetic nanoparticles coated with PEG or CMDx are highly stable in water at pH 7 and in the presence of electrolytes such as NaCl, which makes these modified magnetic nanoparticles attractive for biological applications such as magnetic fluid hyperthermia for cancer treatment or as MRI contrast agents. This work was supported by the US National Science Foundation (Grants CBET-0329374, DMR-0351449, and OIA-0701525), NASA (NCC5-595). We are grateful to the Integrated Advanced Microscopy facility at the Cornell Center for Materials Research (CCMR) supported by the NSF–MRSEC program (NSF DMR-0520404) and Prof. Juan Hinestroza and Alejandra Andere for performing TEM measurements.
0
-20
-40
1399
References
0.00 0.02 0.04
0.06 0.08 0.10 0.12 0.14 0.16
[NaCl] Fig. 4. Zeta potential for (a) magnetite–PEG and (b) magnetite–CMDx nanoparticles as a function of NaCl concentration in water at pH 7.
the surface charge changed to negative due to the presence of unreacted carboxyl groups remaining in CMDx grafted to the particle. In this case, the observed pI shifted to 2.5 with no particle precipitation over the entire pH range. For particles coated with PEG–COOH, the particle surface charge switches from a positive charge at pH below 7 to negative at pH above 7. In this case, the surface charge is attributed to ions adsorbed from solution to the PEG layer on the particle surface [13]. No precipitation was observed over the entire pH range for the PEG-coated nanopar-
[1] Q.A. Pankhurst, J. Connolly, S.K. Jones, J. Dobson, J. Phys. D: Appl. Phys. 36 (2003) R167. [2] C.C. Berry, A.S.G. Curtis, J. Phys. D: Appl. Phys. 36 (2003) R198. [3] C.C. Berry, The Royal Society of Chemistry 15 (2005) 543. [4] S. Mornet, J. Portier, E. Duguet, J. Magn. Magn. Mater. 293 (2005) 127. [5] E. Parton, R.d. Palma, G. Borghs, Nanotechnology (2007) 47. [6] A.P. Herrera, C. Barrera, C. Rinaldi, J. Mater. Chem. 18 (2008) 3650. [7] J. Park, K. An, Y. Hwang, et al., Nature 3 (2004) 891. [8] N. Nakajima, Y. Ikada, Bioconjugate Chem. 6 (1994) 123. [9] B.S. Lele, M.G. Kulkarni, J. Appl. Polym. Sci. 70 (1998) 883. [10] L. Zhang, R. He, H. Gu, Appl. Surf. Sci. 253 (2006) 2611. [11] K. Bierbaum, M. Kinzler, C. Woll, M. Grunze, Langmuir 11 (1995) 512. [12] D. Lin-Vien, N. Colthup, W. Fateley, J. Graselli, The Handbook of Infrared and Raman Characteristic Frequencies of Organic Molecules, Academic Press, San Diego, 1991. [13] R.d. Palma, S. Peeters, J.M.V. Bael, et al., Chem. Mater. 19 (2007) 1821. [14] P.C. Hiemenz, R. Rajagopalan, Principles of colloid and surface chemistry. Marcel Dekker, New York. [15] R. Chantrell, J. Popplewell, S. Charles, IEEE Trans. Magn. 14 (1978) 975.