Radioprotective Effects of Manganese Oxide Nanoparticles in the Mice Exposed to High Doses of γ-Radiation
Доклады на конференциях
Nowadays, malignant brain tumors are one of the most complex oncological diseases for therapeutic intervention. While radiotherapy is a powerful anticancer treatment approach, it is associated with severe side effects that drastically limit its therapeutic capacity. Since, the killing of cells by radiation is mediated by the ionization of irradiated matter, development of radioprotective agents which would be substantially improved the outcome of radiotherapy without an increase in the radioresistance of tumors is a one of the most important problems in the conduct of radiation therapy.
Previously, it was showed the ability of nanoparticles of manganese oxide to accumulate in the animal's body. Toxic effects of nanoparticles were shown to be in a high dependence on particle size and morphology. For example, particles of a cubic shape and sizes of 50-200 nm have a minimal toxic effect and are able to accumulate in the brain. So, the aim of this stuy was to investigate the effects of nanoparticles on living tissues exposed to ionizing radiation. Using irradiation in doses close to clinical and several times exceeding them, in mouse model it was shown the high radioprotective activity of manganese oxide nanoparticles. In group of animals with head-only irradiation in a dose of 100 Gy, intraperitoneal injection of manganese oxide nanoparticles increase the survival rate from 69% to 100%. With the increase in the irradiation dose to 200 Gy, the protective effects of the nanoparticles are also preserved, but after head-only irradiation in a dose of 400 Gy all animals died within a few hours.
Thus, we hypothesized that the mechanism of protective action of manganese oxide nanoparticles is associated with free radicals scavenging. Using hyperoxia animal pretreatment for enhancement of superoxide radical production during irritation, ROS-scavenging properties of manganese oxide nanoparticle were confirmed. In group of animals exposed to hyperoxia before head-only irradiation in a dose of 200 Gy, intraperitoneal injection of manganese oxide nanoparticles increase the survival rate from 16% to 67%. Thus, we are the first ones to show in vivo the radioprotective effects of manganese nanoparticles.