Biomineralized Manganese Oxide Nanoparticles Synergistically Relieve Tumor Hypoxia and Activate Immune Response with Radiotherapy in Non-Small Cell Lung Cancer.

Radiotherapy (RT) is currently considered as an essential treatment for non-small cell lung cancer (NSCLC); it can induce cell death directly and indirectly via promoting systemic immune responses. However, there still exist obstacles that affect the efficacy of RT such as tumor hypoxia and immunosuppressive tumor microenvironment (TME). Herein, we report that the biomineralized manganese oxide nanoparticles (Bio-MnO 2 NPs) prepared by mild enzymatic reaction could be a promising candidate to synergistically enhance RT and RT-induced immune responses by relieving tumor hypoxia and activating cGAS-STING pathway. Bio-MnO 2 NPs could convert endogenic H 2 O 2 to O 2 and catalyze the generation of reactive oxygen species so as to sensitize the radiosensitivity of NSCLC cells. Meanwhile, the release of Mn 2+ into the TME significantly enhanced the cGAS-STING activity to activate radio-immune responses, boosting immunogenic cell death and increasing cytotoxic T cell infiltration. Collectively, this work presents the great promise of TME reversal with Bio-MnO 2 NPs to collaborate RT-induced antitumor immune responses in NSCLC.