Light-triggered nanocarriers modulate mitochondrial metabolism for enhancing anti-tumor immune response

Dysfunctional mitochondria in tumor cells result cellular metabolic reprogramming, which is major element in tumor immune evasion. Therefore, normalization of mitochondrial function in tumor cells as an emerging target for improving the immunosuppressive tumor microenvironment in favor of tumor immunotherapy. Herein, a photosynergistic Mitochondrial metabolism nanoregulator (Mito-MNR) was constructed based on thylakoid (TK) membrane and Hollow mesoporous MnO2 to augment the tumor immune response by regulating the mitochondrial function of tumor cells. Under near infrared light irradiation, TK balanced mitochondrial oxidative phosphorylation and glycolysis via producing NADPH and ATP, which significantly boosted the function of tumor-infiltrating cytotoxic T cells. In addition, HM highly increased NADPH production through amplifying photosynthesis in thylakoids as an electron acceptor. Overall, the developed Mito-NMR offer a reliable strategy to strengthen the immune response of tumors by photo-modulating tumor mitochondria to ameliorate in situ tumor metabolic-immune intrinsic response.