The therapeutic efficacy of photodynamic therapy (PDT) is usually limited by the hypoxia problem in the tumor microenvironment (TME). Real-time monitoring of 1O2, the most important reactive oxygen species (ROS) in PDT, is essential for assessing PDT efficacy and optimizing treatment regimens. Herein, a versatile therapeutic and sensing nanoplatform was designed and constructed, which integrated PDT efficacy amplification, oxygen (O2) self-supply, and intracellular 1O2 self-monitoring. The anthracene-based 1O2 sensitive fluorophore (H4adip) was encapsulated into the porphyrin metal-organic skeleton (PCN-222) and a CeO2 nanozyme was modified on the surface by L-arginine to synthesize H4adip@PCN-222@CeO2 (HPC). In this nanoplatform, PCN-222 was used as a photosensitizer to interact with O2 under laser irradiation to generate 1O2, thereby exerting the native anti-tumor effect of PDT. CeO2 acted as a nanozyme with peroxidase- and catalase-like characteristics that underwent a Fenton-like reaction with excess hydrogen peroxide (H2O2) in the TME to generate O2 and hydroxyl radicals (·OH). The generated O2 can alleviate tumor hypoxia and overcome the limitation of PDT efficacy caused by the hypoxic tumor microenvironment, while the ·OH can be used for chemodynamic therapy (CDT). The O2 generated by the Fenton-like reaction served as the supplementary raw material for the PDT reaction, while the generated cytotoxic ·OH killed the tumor cells. The proposed multifunctional nanoplatform broke through the limitations of single therapy and effectively eliminated the tumor cells. In addition, the H4adip probe monitored the generation of 1O2 through fluorescence imaging and the PDT process was evaluated in real time. The versatile nanoplatform provides an innovative strategy for more effective elimination of tumor cells and accurate assessment of PDT efficacy in clinical practice.
Li et al. (Thu,) studied this question.