Ultrafast Fabrication of Iron/Manganese Co-Doped Bismuth Trimetallic Nanoparticles: A Thermally Aided Chemodynamic/Radio-Nanoplatform for Low-Dose Radioresistance

Low-dose radioresistance continues to be one of the major limitations for clinical curative treatment of cancer. Luckily, nanotechnology mediated by multifunctional nanomaterials provides potential opportunity to relieve the radioresistance via increasing the radiosensitivity of cancer cells. Herein, an ultrafast fabrication strategy is reported to prepare iron/manganese co-doped bismuth trimetallic nanoparticles (pFMBi NPs) as a multifunctional radiosensitizer for combined therapy. The bismuth matrix provides the intrinsic radiosensitization effect under the low and safe radiation dose via Auger electrons, photoelectrons, and Rayleigh scattering. Meanwhile, co-doping of iron and manganese ions endows pFMBi NPs with both the Fenton reaction property for reactive oxygen species (ROS) generation and photothermal conversion performance for heat production. Additional ROS generation enhances the radiosensitization effect by collaborating with Rayleigh scattering-mediated water radiolysis, and endogenous heat production under near-infrared 808 nm laser irradiation makes DNA more sensitive to radiation and ROS damage. Both in vitro and in vivo evaluations demonstrate the effective antitumor and radiosensitization effects via thermally aided chemodynamic/radiotreatment with a low radiation dose (6 Gy). Therefore, this work provides a potential strategy for overcoming the low-dose radioresistance in cancer therapy.