Calcium peroxide nanoparticles induce endoplasmic reticulum stress for enhanced radiation therapy of osteosarcoma

Radiation therapy (RT) has been widely used in clinics. The expression of various radiation-resistant proteins limits the curative effect of RT. Endoplasmic reticulum (ER) plays a critical role in the synthesis of these proteins. In this work, CaO2 nanoparticles (NPs) were applied to interfere with the function of ER as radiosensitizers for RT. After endocytosis by tumor cells, the CaO2 NPs in tumor microenvironment will release excessive Ca2+ and H2O2, which could induce ER stress, impair the expression of radiation-resistant proteins, and finally enhance the effect of RT. Both in vitro and in vivo results prove the favorable performance of CaO2 NPs in inducing ER stress with a pathway of the downstream thioredoxin system, which improves the yield of reactive oxygen species (ROS) generated by RT to strengthen its curative effect. This study brings a new radio-sensitizing strategy for radiotherapy which may expand its application in medicine.