Water Dispersible CoFe2O4 Nanoparticles With Improved Colloidal Stability for Biomedical...

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Water dispersible CoFe 2 O 4 nanoparticles with improved colloidal stability for biomedical applications Sandeep Munjal a , Neeraj Khare a,n , Chetan Nehate b , Veena Koul b a Department of Physics, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India b Centre for Biomedical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India article info Article history: Received 29 October 2015 Received in revised form 16 November 2015 Accepted 2 December 2015 Available online 7 December 2015 Keywords: CoFe 2 O 4 Biomedical applications Ligand exchange Superparamagnetism Nanoparticles abstract Single phase cobalt ferrite (CoFe 2 O 4 , CFO) nanoparticles of a controlled size (6 nm) exhibiting super- paramagnetic properties have been synthesized by hydrothermal technique using oleic acid (OA) as surfactant. The oleic acid coated CFO nanoparticles are stable in non-polar organic media, such as hexane but are not well dispersible in water. The surface of these nanoparticles has been further modied by citric acid using ligand exchange process, which makes CFO nanoparticles more stable colloidal solution in water. Citric acid coated CFO nanoparticles exhibits high dispersibility in water, high zeta potential, very low coercivity and moderate saturation magnetization. Biocompatibility of these CFO nanoparticles is demonstrated through cytotoxicity test in L929 cell line. & 2015 Elsevier B.V. All rights reserved. 1. Introduction In recent years magnetic nanoparticles have been extensively explored for their potentiality in many biomedical applications such as for targeted drug delivery [1], as contrast enhancement agents in magnetic resonance imaging (MRI) [2], and in hy- perthermia treatments as heat mediators [3]. The main advantage of magnetic nanoparticles for biomedical applications is its larger surface area for easy ligand attachment, better tissue diffusion and reduced dipoledipole interaction. The magnetic properties of the nanoparticles can be tuned by controlling its size [4], composition [5], shape [6] and strain/defects [7]. By carefully reducing its size below to a critical diameter, the magnetic nanoparticles can be turned to superparamagnetic nanoparticles. Iron oxide magnetic nanoparticles such as Fe O 3 4 [2] and γ−Fe O 2 3 [8] have been widely explored for biomedical applications. The saturation magnetization and hysteresis losses of these iron oxide nanoparticles are small compared to pure metals (Co, Fe, or CoFe etc.), but the metallic nanoparticles are highly toxic and very sensitive to oxidation and hence are not useful for biomedical applications. Another alternative can be spinel ferrites such as MFe 2 O 4 (MCo, Mn, Ni) [911]. Among these ferrites, CoFe 2 O 4 is interesting due to its large curie temperature, high effective anisotropy and moderate saturation magnetization [12]. CFO has an inverse spinel structure with general formula AB 2 O 4 (A ¼ Fe and B ¼ Co, Fe) where half of the Fe 3 þ occupies the octahedral sites and the other half Fe 3 þ occupies the tetrahedral sites whereas all the Co 2 þ occupy the octahedral sites. For biomedical applications the magnetic nanoparticles should be of small sizes with narrow size distribution. These nano- particles should be coated with some organic or inorganic material which ensure their biocompatibility, nontoxicity and colloidal stability in biophase. Several techniques such as microemulsion [13], coprecipitation [14], ball milling [15], solgel [16], thermal decomposition [17], sonochemical [18] and electrosynthesis [9] method have been employed for the synthesis of magnetic nano- particles but all these synthesis methods often produce larger size nanoparticles with wide particle size distribution. In the present work, we have synthesized uniform size (6 nm) CoFe 2 O 4 magnetic nanoparticles using hydrothermal techniques with oleic acid as surfactant. These oleic acid coated CFO nano- particles are not dispersible in water and in order to make these nanoparticles water dispersible, the surface of these oleic acid coated nanoparticles was modied with citric acid using ligand exchange method. It is found that these citric acid coated CoFe 2 O 4 nanoparticles makes a good colloidal solution in water in a wide range of pH. The biocompatibility of citric acid coated CFO nano- particles was studied with mouse broblast L929 cells lines, using a MTT cytotoxicity assay. Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/jmmm Journal of Magnetism and Magnetic Materials http://dx.doi.org/10.1016/j.jmmm.2015.12.017 0304-8853/& 2015 Elsevier B.V. All rights reserved. n Corresponding author. E-mail address: [email protected] (N. Khare). Journal of Magnetism and Magnetic Materials 404 (2016) 166169

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Single phase cobalt ferrite (CoFe2O4, CFO) nanoparticles of a controlled size (∼6 nm) exhibiting superparamagnetic properties have been synthesized by hydrothermal technique using oleic acid (OA) as surfactant. The oleic acid coated CFO nanoparticles are stable in non-polar organic media, such as hexane but are not well dispersible in water. The surface of these nanoparticles has been further modified by citric acid using ligand exchange process, which makes CFO nanoparticles more stable colloidal solution in water. Citric acid coated CFO nanoparticles exhibits high dispersibility in water, high zeta potential, very low coercivity and moderate saturation magnetization. Biocompatibility of these CFO nanoparticles is demonstrated through cytotoxicity test in L929 cell line.

Transcript of Water Dispersible CoFe2O4 Nanoparticles With Improved Colloidal Stability for Biomedical...

Page 1: Water Dispersible CoFe2O4 Nanoparticles With Improved Colloidal Stability for Biomedical Applications

Journal of Magnetism and Magnetic Materials 404 (2016) 166–169

Contents lists available at ScienceDirect

Journal of Magnetism and Magnetic Materials

http://d0304-88

n CorrE-m

journal homepage: www.elsevier.com/locate/jmmm

Water dispersible CoFe2O4 nanoparticles with improved colloidalstability for biomedical applications

Sandeep Munjal a, Neeraj Khare a,n, Chetan Nehate b, Veena Koul b

a Department of Physics, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, Indiab Centre for Biomedical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India

a r t i c l e i n f o

Article history:Received 29 October 2015Received in revised form16 November 2015Accepted 2 December 2015Available online 7 December 2015

Keywords:CoFe2O4

Biomedical applicationsLigand exchangeSuperparamagnetismNanoparticles

x.doi.org/10.1016/j.jmmm.2015.12.01753/& 2015 Elsevier B.V. All rights reserved.

esponding author.ail address: [email protected] (N. K

a b s t r a c t

Single phase cobalt ferrite (CoFe2O4, CFO) nanoparticles of a controlled size (∼6 nm) exhibiting super-paramagnetic properties have been synthesized by hydrothermal technique using oleic acid (OA) assurfactant. The oleic acid coated CFO nanoparticles are stable in non-polar organic media, such as hexanebut are not well dispersible in water. The surface of these nanoparticles has been further modified bycitric acid using ligand exchange process, which makes CFO nanoparticles more stable colloidal solutionin water. Citric acid coated CFO nanoparticles exhibits high dispersibility in water, high zeta potential,very low coercivity and moderate saturation magnetization. Biocompatibility of these CFO nanoparticlesis demonstrated through cytotoxicity test in L929 cell line.

& 2015 Elsevier B.V. All rights reserved.

1. Introduction

In recent years magnetic nanoparticles have been extensivelyexplored for their potentiality in many biomedical applicationssuch as for targeted drug delivery [1], as contrast enhancementagents in magnetic resonance imaging (MRI) [2], and in hy-perthermia treatments as heat mediators [3]. The main advantageof magnetic nanoparticles for biomedical applications is its largersurface area for easy ligand attachment, better tissue diffusion andreduced dipole–dipole interaction. The magnetic properties of thenanoparticles can be tuned by controlling its size [4], composition[5], shape [6] and strain/defects [7]. By carefully reducing its sizebelow to a critical diameter, the magnetic nanoparticles can beturned to superparamagnetic nanoparticles.

Iron oxide magnetic nanoparticles such as Fe O3 4 [2] andγ−Fe O2 3 [8] have been widely explored for biomedical applications.The saturation magnetization and hysteresis losses of these ironoxide nanoparticles are small compared to pure metals (Co, Fe, orCoFe etc.), but the metallic nanoparticles are highly toxic and verysensitive to oxidation and hence are not useful for biomedicalapplications. Another alternative can be spinel ferrites such asMFe2O4 (M≅Co, Mn, Ni) [9–11]. Among these ferrites, CoFe2O4 isinteresting due to its large curie temperature, high effective

hare).

anisotropy and moderate saturation magnetization [12]. CFO hasan inverse spinel structure with general formula AB2O4 (A¼Fe andB¼Co, Fe) where half of the Fe3þ occupies the octahedral sites andthe other half Fe3þ occupies the tetrahedral sites whereas all theCo2þ occupy the octahedral sites.

For biomedical applications the magnetic nanoparticles shouldbe of small sizes with narrow size distribution. These nano-particles should be coated with some organic or inorganic materialwhich ensure their biocompatibility, nontoxicity and colloidalstability in biophase. Several techniques such as microemulsion[13], coprecipitation [14], ball milling [15], sol–gel [16], thermaldecomposition [17], sonochemical [18] and electrosynthesis [9]method have been employed for the synthesis of magnetic nano-particles but all these synthesis methods often produce larger sizenanoparticles with wide particle size distribution.

In the present work, we have synthesized uniform size (∼6 nm)CoFe2O4 magnetic nanoparticles using hydrothermal techniqueswith oleic acid as surfactant. These oleic acid coated CFO nano-particles are not dispersible in water and in order to make thesenanoparticles water dispersible, the surface of these oleic acidcoated nanoparticles was modified with citric acid using ligandexchange method. It is found that these citric acid coated CoFe2O4

nanoparticles makes a good colloidal solution in water in a widerange of pH. The biocompatibility of citric acid coated CFO nano-particles was studied with mouse fibroblast L929 cells lines, usinga MTT cytotoxicity assay.