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Dextran and Polymer Polyethylene Glycol (PEG) Coating Reduce Both 5 and 30 nm Iron Oxide Nanoparticle Cytotoxicity in 2D and 3D Cell Culture
Mechanical Engineering and Mechanics Department, Drexel University, Philadelphia, PA 19104, USA
Institute for Environmental Medicine and Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
* Author to whom correspondence should be addressed.
Received: 15 February 2012; in revised form: 15 April 2012 / Accepted: 30 April 2012 / Published: 9 May 2012
Abstract: Superparamagnetic iron oxide nanoparticles are widely used in biomedical applications, yet questions remain regarding the effect of nanoparticle size and coating on nanoparticle cytotoxicity. In this study, porcine aortic endothelial cells were exposed to 5 and 30 nm diameter iron oxide nanoparticles coated with either the polysaccharide, dextran, or the polymer polyethylene glycol (PEG). Nanoparticle uptake, cytotoxicity, reactive oxygen species (ROS) formation, and cell morphology changes were measured. Endothelial cells took up nanoparticles of all sizes and coatings in a dose dependent manner, and intracellular nanoparticles remained clustered in cytoplasmic vacuoles. Bare nanoparticles in both sizes induced a more than 6 fold increase in cell death at the highest concentration (0.5 mg/mL) and led to significant cell elongation, whereas cell viability and morphology remained constant with coated nanoparticles. While bare 30 nm nanoparticles induced significant ROS formation, neither 5 nm nanoparticles (bare or coated) nor 30 nm coated nanoparticles changed ROS levels. Furthermore, nanoparticles were more toxic at lower concentrations when cells were cultured within 3D gels. These results indicate that both dextran and PEG coatings reduce nanoparticle cytotoxicity, however different mechanisms may be important for different size nanoparticles.
Keywords: endothelial cells; cytotoxicity; superparamagnetic iron oxide nanoparticles; dextran; PEG; reactive oxygen species; 3D cell culture
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Yu, M.; Huang, S.; Yu, K.J.; Clyne, A.M. Dextran and Polymer Polyethylene Glycol (PEG) Coating Reduce Both 5 and 30 nm Iron Oxide Nanoparticle Cytotoxicity in 2D and 3D Cell Culture. Int. J. Mol. Sci. 2012, 13, 5554-5570.
Yu M, Huang S, Yu KJ, Clyne AM. Dextran and Polymer Polyethylene Glycol (PEG) Coating Reduce Both 5 and 30 nm Iron Oxide Nanoparticle Cytotoxicity in 2D and 3D Cell Culture. International Journal of Molecular Sciences. 2012; 13(5):5554-5570.
Yu, Miao; Huang, Shaohui; Yu, Kevin Jun; Clyne, Alisa Morss. 2012. "Dextran and Polymer Polyethylene Glycol (PEG) Coating Reduce Both 5 and 30 nm Iron Oxide Nanoparticle Cytotoxicity in 2D and 3D Cell Culture." Int. J. Mol. Sci. 13, no. 5: 5554-5570.