Versatile MOFs with dual-enzyme-mimetic activities for cancer hypoxia relief and assisted photodynamic therapy upon fluorescence imaging

Abstract

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.