Cell toxicity of superparamagnetic iron oxide nanoparticles M. Mahmoudi a, * , A. Simchi a,b , A.S. Milani c , P. Stroeve d a Institute for Nanoscience and Nanotechnology, Sharif University of Technology, Tehran, Iran b Department of Material Science and Engineering, Sharif University of Technology, Tehran, Iran c School of Engineering, University of British Columbia Okanagan, Canada d Department of Chemical Engineering and Materials Science, University of California Davis, Davis, CA 95616, USA article info Article history: Received 19 February 2009 Accepted 8 April 2009 Available online 22 April 2009 Keywords: Superparamagnetic nanoparticles Magnetite Polyvinyl alcohol Polymeric nanocomposite MTT assay Cell toxicity abstract The performance of nanoparticles for biomedical applications is often assessed by their narrow size dis- tribution, suitable magnetic saturation and low toxicity effects. In this work, superparamagnetic iron oxide nanoparticles (SPIONs) with different size, shape and saturation magnetization levels were synthe- sized via a co-precipitation technique using ferrous salts with a Fe 3+ /Fe 2+ mole ratio equal to 2. A para- metric study is conducted, based on a uniform design-of-experiments methodology and a critical polymer/iron mass ratio (r-ratio) for obtaining SPION with narrow size distribution, suitable magnetic saturation, and optimum biocompatibility is identified. Polyvinyl alcohol (PVA) has been used as the nanoparticle coating material, owing to its low toxicity. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltet- razolium bromide (MTT) assay is used to investigate the cell biocompatibility/toxicity effects of the sam- ples. From the MTT assay results, it is observed that the biocompatibility of the nanoparticles, based on cell viabilities, can be enhanced by increasing the r-ratio, regardless of the stirring rate. This effect is mainly due to the growth of the particle hydrodynamic size, causing lower cell toxicity effects. Ó 2009 Elsevier Inc. All rights reserved. 1. Introduction Superparamagnetic iron oxide nanoparticles (SPIONs) have po- tential biomedical applications such as magnetic drug targeting, enhanced resolution magnetic resonance imaging, tissue repair, cell and tissue targeting and transfection [1–5]. Superparamagnet- ism in many biomedical applications such as drug delivery is useful because the SPION can be transported by electrical field effects to the desired site and once the external magnetic field is removed, magnetization disappears and the SPION can remains at the target site for a certain period. Several methods such as arc discharge, mechanical grinding, la- ser ablation, microemulsions and high temperature decomposition of organic precursors have been reported for the synthesis of Fe 3 O 4 nanoparticles [6]. The chemical coprecipitation method is a com- mon technique used to produce dispersed (water-based) Fe 3 O 4 nanoparticles at low temperatures. If a suitable surfactant is em- ployed and the processing parameters (pH, reaction temperature, stirring rate, solute concentration, etc.) are controlled, the size, dis- tribution and shape of the particles can be tailored [7–10]. Individ- ual nanoparticles and nanoparticle agglomerates can be characterized by the magnetic core size and the hydrodynamic diameter. The parameters are important for targeting purposes. The first one is responsible for the magnetic response in applied inhomogeneous magnetic fields and the second parameter is important for targeting and cell interactions [11]. A coating layer can prevent the agglomeration of the particles, increase the circu- lation time, and provide biocompatibility. Monodispersed particles with a high saturation magnetization and functionalized with suit- able coatings are required for targeting and imaging in hyperther- mia, transfection and MRI (magnetic resonance imaging) applications. Despite the pros and cons of using nanoscale iron oxides for in vivo applications, superparamagnetic iron oxide nanoparticles (SPIONs) remain the only magnetic nanoparticles that have been approved for clinical use to date [12]. Investigators seeking fast- track developments of magnetic-guided therapy often prefer this tried-and-tested option. One solution to the nanoparticles’ weak magnetic responsiveness is to maximize the magnetic field at the target sites [12]. It has been recognized that the core size of iron oxide nanoparticles determines the magnetic properties; however, less work has been conducted to investigate the effect of hydrody- namic size on magnetic properties [13]. Recently, we have reported the effect of both stirring rate and base molarities variations on the characteristics of superparamagnetic nanoparticles with the reac- tion temperature fixed at 35 °C [14]. The aim of the present work is to study the effect of other important synthesis parameters including polymer/iron mass ra- tion and homogenization rate while the reaction temperature is not fixed. The temperature changes via the heat produced by the 0021-9797/$ - see front matter Ó 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jcis.2009.04.046 * Corresponding author. Fax: +1 530 752 1031. E-mail addresses: mahmoudi@mehr.sharif.edu (M. Mahmoudi), pstroeve@ucda- vis.edu (P. Stroeve). Journal of Colloid and Interface Science 336 (2009) 510–518 Contents lists available at ScienceDirect Journal of Colloid and Interface Science www.elsevier.com/locate/jcis