Normalizing Tumor Microenvironment Based on Photosynthetic Abiotic/Biotic Nanoparticles

Tumor hypoxia has attained the status of a core hallmark of cancer that globally affects the entire tumor phenotype. Reversing tumor hypoxia might offer alternative therapeutic opportunities for current anticancer therapies. In this research, a photosynthetic leaf-inspired abiotic/biotic nano-thylakoid (PLANT) system was designed by fusing the thylakoid membrane with synthetic nanoparticles for efficient O₂ generation <i>in vivo</i>. Under 660 nm laser irradiation, the PLANT system exhibited intracellular O₂ generation and the anaerobic respiration of the multicellular tumor spheroid was suppressed by PLANT as well. <i>In vivo</i>, it was found that PLANT could not only normalize the entire metabolic network but also adjust the abnormal structure and function of the tumor vasculature. It was demonstrated that PLANT could significantly enhance the efficacy of phototherapy or antiangiogenesis therapy. This facile approach for normalizing the tumor microenvironment will find great potential in tumor therapy