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 MnO2 (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 Mn2+, but is also beneficial for sustainably generating O-2 via composition of excessive H2O2 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.

Automated summary

Researchers have developed an intelligent nanoplatform that can efficiently treat hypoxic tumors by persistently utilizing oxygen. The nanoplatform releases inhibitors and excess H2O2 to generate oxygen continuously, and enhances photodynamic therapy through the activation of a photosensitizer using X-ray irradiation. This method offers sustained and improved treatment for hypoxic tumors.