An intelligent persistent luminescence nanoplatform with high-efficiency O2 utilization for continuous hypoxic tumors treatment

Hypoxia, which emerges in most solid tumors, significantly restricts therapeutic effect during treatment. To date, many smart nanoparticles that continuously generate O 2 have been developed to relieve hypoxia in tumors. Nevertheless, the short therapy duration resulting from the intrinsic properties of these nanoparticles left the subsequently generated O 2 not to be fully utilized, resulting in suboptimal treatment. Here, by loading mesopore MnO 2 (mMnO 2 ), photosensitizer and carbonic anhydrase IX inhibitor (CAI) on persistent luminescence nanoparticles (PLNPs), we designed an intelligent nanoplatform that can persistently exploit O 2 for efficient treatment of hypoxic tumors. In the tumor microenvironment, CAI is released rapidly as a result of degradation of mMnO 2 , reducing the intracellular pH value to accelerate the degradation process. This is not only advantageous for drug release and chemodynamic therapy (CDT) via released Mn 2+ , but is also beneficial for sustainably generating O 2 via composition of excessive H 2 O 2 to relieve hypoxia. With X-ray irradiation, the photosensitizer is activated by PLNPs, consuming generated O 2 to realize enhanced photodynamic therapy. Moreover, after cessation of X-ray irradiation, this process continues, achieving sustained and improved therapy for hypoxic tumors. By exploiting this method, we propose a new treatment methodology for hypoxic tumors.