Engineering Lipid peroxidation reaction in Hyperoxia Microenvironment for Overcome of Tumor Resistance

Apoptosis dysregulation is an important mechanism responsible for the intrinsic and acquired resistances of melanoma, which necessitates the exploration of oncological treatments to activate non-apoptotic cell deaths. Herein, we engineered a lipid peroxidation reaction in hyperoxia tumor microenvironment for induction of ferroptosis and overcome of melanoma resistances. The hyperoxia microenvironment was deliberately constructed by implants of photosynthetic microcapsules (PMCs) consisting of cyanobacteria and upconversion nanoparticles for photosynthesis in chloroplast driven by external near infrared photons. Combination of PMCs and X rays evoked a lipid peroxidation reaction and ferroptosis in melanoma cells and xenografts. Consequently, the intrinsic and acquired resistances in melanoma could be overcome by the engineered reaction, which further contributed to the amelioration of tumor metastases and improvement of survival rates in melanoma-bearing mice. Overall, our findings provide opportunities to overcome melanoma resistances by engineered biochemical reactions and will inspire the exploration of oncological treatments.