Delivered by Ingenta to: University of South Carolina IP: 46.161.61.120 On: Fri, 27 May 2016 10:56:56 Copyright: American Scientific Publishers Copyright © 2013 American Scientific Publishers All rights reserved Printed in the United States of America Article Journal of Biomedical Nanotechnology Vol. 9, 1556–1569, 2013 www.aspbs.com/jbn Dynamic Investigation of Interaction of Biocompatible Iron Oxide Nanoparticles with Epithelial Cells for Biomedical Applications Alice Panariti 1† , Barbara Lettiero 1† , Rodica Alexandrescu 2 , Maddalena Collini 3 , Laura Sironi 3 , Munish Chanana 4 , Ion Morjan 2 , Dayan Wang 5 , Giuseppe Chirico 3 , Giuseppe Miserocchi 3 , Cecilia Bucci 6 , and Ilaria Rivolta 1 ∗ 1 Department of Health Science, New Square of the University, 1-20126, Milan, Italy 2 National Institute for Lasers, Plasma and Radiation Physics, Bucharest, 077125, Romania 3 Department of Physics, University of Milano Bicocca, Milano, 20126, Italy 4 Max Plank Institute of Colloids and Interfaces, Potsdam, 14476, Germany 5 Ian Wark Research Institute, University of South Australia, Adelaide, 5095, Australia 6 Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, 73100, Italy Magnetic nanoparticles have emerged as important players in current research in modern medicine since they can be used in medicine for diagnosis and/or therapeutic treatment of diseases. Among many therapeutic applications of iron-based nanoparticles, drug delivery and photothermal therapy are of particular interest. At cellular level their uptake has been studied and the mechanism by which nanoparticles enter into the cell has important implication not only for their fate but also for their impact on the biological systems. We present here a dynamic investigation of interaction of biocom- patible iron oxide nanoparticles coated with L-3,4-dihydroxyphenylalanine and labeled with tetra-methylrhodamine-5/6- isothiocyanate with lung epithelial cells. Our data show that after macropinocytosis-mediated internalization, nanoparticles in form of vesicles approach the nucleus and converge in the more acidic compartments of the cells in a microtubule- dependent manner. During progression the nanoparticles aggregate. Finally, we have demonstrated that a converging laser radiation on the cells, causes the increase in the local temperature and thus damages the cells, suggesting that these nanoparticles may be applied for photothermal therapy studies. KEYWORDS: Iron Oxide Nanoparticles, Nanoparticles Uptake, Intracellular Trafficking, Photothermal Therapy, Nanomedicine, Bio- compatibility, Macropynocitosis. INTRODUCTION Superparamagnetic iron oxide nanoparticles (NPs) have been intensively developed for their scientific interest in many technological applications, in vitro and in vivo. 1 As far as concerned their medical applications, mag- netic NPs can be used for diagnosis and/or therapeu- tic treatment of diseases. Thanks to their paramagnetic properties, they are currently employed as contrast agents ∗ Author to whom correspondence should be addressed. Email: ilaria.rivolta@unimib.it † These two authors contribute to this paper equally. Received: 4 February 2013 Accepted: 27 March 2013 in magnetic resonance imaging (MRI) for targeting organs (liver and spleen) or lymph nodes, 2 3 gather in vivo infor- mation about tumour status 4 5 or tracking of mesenchy- mal stem cells (MSC) for future MSCs-based stem cell therapy. 6 Among many therapeutic applications of iron-based NPs, drug delivery and photothermal therapy are of par- ticular interest. In order to be applied, iron oxide NPs must be smaller than red blood cells, non-cytotoxic and non-immunogenic. 7 Moreover, the interaction between nanoparticles and plasma membrane, and their intracellular behaviour, are widely influenced by different processes of synthesis, stabilization and surface modification. 8–11 Like other nanomaterial-based systems, the NP surfaces must 1556 J. Biomed. Nanotechnol. 2013, Vol. 9, No. 9 1550-7033/2013/9/1556/014 doi:10.1166/jbn.2013.1668