Iron Oxide Nanoparticles as Enhancers for Radiotherapy of Tumors.

Abstract

This research aimed to evaluate the potency of preparation based on heparinized iron oxide nanoparticles (hIONPs) in combination with radiation therapy, including magnetic delivery via the applied magnetic field (AMF), in sarcoma and cervical cancer models. For in vitro studies, cells of rhabdomyosarcoma (RD), fibrosarcoma (HT1080), and cervical cancer (HeLa S3) were treated with hIONPs and analyzed for survival rate and hIONP uptake. Then, cell morphology, cell cycle, increase of reactive oxygen species, mitochondria depolarization, and ability to form colonies were assessed for combined treatment (hIONPs + 3Gy). For in vivo research, hIONPs were administered once in the hybrids of CBAxC57Bl/6j mice, grafted with sarcoma (S37) and cervical cancer (CC5) strains. The ultimate in vivo treatment modes were: (1) i.v. hIONPs (14 μg/kg) + 5 Gy; (2) i.v. hIONPs (14 μg/kg) + AMF + 5 Gy; and (3) i.t. hIONPs (2,8 μg/kg) + 5 Gy. The overall survival rates, increase in life expectancy, inhibition of tumor growth (tumor growth inhibition), and degree of inhibition (T/C) were determined, and pathomorphological changes were assessed in experimental groups. The combined treatment in vitro (hIONPs + 3Gy) promotes multiple tumor cell death with high-severity peroxide effects compared with other groups. The sarcoma cells were more sensitive than cervical cancer cells. For in vivo, an enhancing effect was revealed by the combination of radiotherapy and magnetic-delivered hIONPs. For S37 tumor, the treatment regimen was characterized as having a high antitumor effect, ≪++++ ≫, with a 20% cure rate of mice. For the CC5 tumor, the effect was accompanied by the inhibition of tumor growth, an increase in the life expectancy of animals, and was characterized as a significant antitumor effect, ≪+++/++ ≫. From the data obtained, it can be concluded that the radiosensitizing potential of hIONPs may be taken as a basis of combined radiation treatment protocols.