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U Altanerova,1 M Babincova,2 P Babinec,2 K Benejova,1 J Jakubechova,1 V Altanerova,1 M Zduriencikova,3 V Repiska,4 C Altaner1,3 1Stem Cell Preparation Department, St Elisabeth Cancer Institute, Bratislava, Slovakia; 2Department of Nuclear Physics and Biophysics, Comenius University, Bratislava, Slovakia; 3Cancer Research Institute, Biomedical Center, Slovak Academy of Sciences, Bratislava, Slovakia; 4Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, Slovakia Abstract: Magnetic hyperthermia, or the heating of tissues using magnetic materials, is a promising approach for treating cancer. We found that human mesenchymal stem cells (MSCs) isolated from various tissues and MSCs expressing the yeast cytosine deaminase::uracil phosphoribosyl transferase suicide fusion gene (yCD::UPRT) can be labeled with Venofer, an iron oxide carbohydrate nanoparticle. Venofer labeling did not affect cell proliferation or the ability to home to tumors. All Venofer-labeled MSCs released exosomes that contained iron oxide. Furthermore, these exosomes were efficiently endocytosed by tumor cells. Exosomes from Venofer-labeled MSCs expressing the yCD::UPRT gene in the presence of the prodrug 5-fluorocytosine inhibited tumor growth in a dose-dependent fashion. The treated tumor cells were also effectively ablated following induction of hyperthermia using an external alternating magnetic field. Cumulatively, we found that magnetic nanoparticles packaged into MSC exosomes are efficiently endocytosed by tumor cells, facilitating targeted tumor cell ablation via magnetically induced hyperthermia. Keywords: mesenchymal stem cells, iron oxide labeling, Venofer, yCD::UPRT-exosomes, yCD::UPRT-MSCs/Fe exosomes, magnetic hyperthermia |
