Characterization and optimization of nano-structures with hyperthermic properties for biomedical applications.

In the last years, our group focused on magnetic nanoparticles (MNPs), which are able to induce hyperthermia, as potential biomedical tools. Magnetic hyperthermia is a term used to denote the generation of heat by MNPs in response to the application of an external alternating magnetic field. We applied hyperthermia in vitro with different aims and the effects on cells were analyzed by applying viability test and morphological analysis with light and transmission electron microscopy (TEM) techniques. We used superparamagnetic iron oxide nanoparticles (NPs) to induce delipidation in 3T3L1 adipocytes and human adipose-derived adult stem cells. Immediately after hyperthermia, we observed a drastic intracellular lipid loss that persisted for at least 24h in the absence of cell death, damage or dedifferentiation. These results open interesting perspectives for the application of hyperthermia to treat obesity. We applied hyperthermic treatment also to cancer cells, known to be more sensitive to heat shock than healthy cells, in order to induce apoptosis. A glioblastoma cell line (U87MG) was treated with either Zn-SPIONs or biomimetic magnetic NPs (BMNPs). Zn-SPIONs are amphiphilic polymer, dodecyl grafted poly(isobutylene-alt-maleic anhydride) coated zinc-doped iron oxide (Fe3O4) NPs of 15±2 nm size, and show a high thermal capacity. BMNPs, synthetized with the protein MamC from magnetotactic bacteria, may act as both drug carriers and hyperthermic agents, being promising tools for the treatment of many types of tumor. BMNPs were also tested in a human hepatocyte carcinoma cell line (HepG2) after functionalizaton with a Choline Kinase inhibitor in order to obtain a nanocarrier potentially suitable for targeted chemotherapy. In fact, Choline Kinase is considered as a biomarker of tumor progression and carcinogenesis, and a target therapy. Therefore, our nanocarriers would allow a local treatment of cancer thus avoiding/reducing possible systemic side effects. The internalization of BMNPs was evaluated using TEM. Taken together, our results prove the efficacy of MNPs in inducing hyperthermia in cultured cells. Although these basic data have been obtained in in vitro models, they suggest the suitability of these NPs as therapeutic tools and encourage further studies for their application in the biomedical field.