FePt/MnO2@PEG Nanoparticles as Multifunctional Radiosensitizers for Enhancing Ferroptosis and Alleviating Hypoxia in Osteosarcoma Therapy.

Radiotherapy (RT) is a widely used cancer treatment, and the use of metal-based nanoradiotherapy sensitizers has demonstrated promise in enhancing its efficacy. However, achieving effective accumulation of these sensitizers within tumors and overcoming resistance induced by the hypoxic tumor microenvironment remain challenging issues. In this study, we developed FePt/MnO₂@PEG nanoparticles with multiple radiosensitizing mechanisms, including high-atomic-number element-mediated radiation capture, catalase-mimicking oxygenation, and GSH depletion-induced ferroptosis. Both in vitro and in vivo experiments were conducted to validate the radiosensitizing mechanisms and therapeutic efficacy of FePt/MnO₂@PEG. In conclusion, this study presents a novel and clinically relevant strategy and establishes a safe and effective combination radiotherapy approach for cancer treatment. These findings hold significant potential for improving radiotherapy outcomes and advancing the field of nanomedicine in cancer therapy.