Demash D. Modulation of cisplatin biological effects with static magnetic field as a part of antitumor nanosystem for target delivery (experimental study)

Thesis is devoted to definining the role of static magnetic field (SMF) in enhancing the antitumor activity of cisplatin in nanocomposite (NC) and determininig the mechanisms underlying its effects in vitro and in vivo. In vitro we showed that 150 mT SMF, starting from 3 h of exposure caused changes in MCF-7 and ascitic Ehrlich carcinoma cells, resulting in development of oxidative stress, damage of DNA structure and functional activity of mitochondria, followed by appropriate cytomorphological changes. It was shown that SMF was able to accelerate the flow of magnetic fluid and NC nanoparticles directly to tumor cells in vitro, what was confirmed by light microscopy. The combined effect of SMF and NC led to a decrease of MCF-7 cells surface charge density and electrokinetic potential. Changes in lipid composition of cell membranes indicated increase of their fluidity and permeability. In addition, observed oxidative stress resulted in changes of mitochondrial activity and in development of genotoxic effects and activation of apoptosis. It was proved that SMF had modulating effects in vivo, significantly enhancing antitumor activity of both cisplatin (by 14.8%) and NC (by 16.2%). Those results were confirmed by morphological and ultrastructural studies of Guerin carcinoma tumor cytoarchitectonics.