H₂O₂/pH Dual-Responsive Biomimetic Nanoenzyme Drugs Delivery System for Enhanced Tumor Photodynamic Therapy

Phototherapy has been recognized as a photochemical process to treat tumor via induce cancer cells necrosis and death, with minimal invasiveness, higher selectivity, and few side effects. However, the therapy effects of phototherapy are often compromised by the hypoxia, high levels of hydrogen peroxide, and glutathione of tumor microenvironment (TME). Therefore, we constructed a catalase-like activity bionic metal-organic framework drugs delivery system (FA-EM@MnO₂/ZIF-8/ICG) with tumor microenvironment controllable releasing. In this system, photosensitizer indocyanine green (ICG) was introduced into zeolite imidazole salt skeleton 8 (ZIF-8) by one-step methods, forming ZIF-8/ICG nano-platform, which can effectively avoid ICG-induced phototoxicity and aggregation-induced quenching during transport. MnO₂ with catalase-like activity was coated on the surface of ZIF-8/ICG nano-platform, which made it have the ability of self-supplying O₂ under the condition of H₂O₂ in TME. Exposure under near-infrared light can alleviate the anoxic TME, thus improving the phototherapy efficiency. In addition, folate-functionalized erythrocyte membrane is coated on the surface of MnO₂/ZIF-8/ICG, which can endow FA-EM@MnO₂/ZIF-8/ICG with the ability of targeted drug administration and immune elimination avoidance. Therefore, FA-EM@MnO₂/ZIF-8/ICG nano-platform has the catalase-like activity, which can alleviate the oxidative stress state of TME and provide a beneficial environment for photodynamic therapy of tumor.