O₂-Generating Metal–Organic Framework-Based Hydrophobic Photosensitizer Delivery System for Enhanced Photodynamic Therapy

Photodynamic therapy (PDT) has been introduced as a photochemical process for treatment by causing cancer cell death and necrosis, with higher accuracy and few side effects. However, the hydrophobicity of most photosensitizers and hypoxia at the tumor sites are two crucial problems to be solved to achieve a successful PDT. Herein, we designed and constructed a novel metal–organic framework-based drug delivery system (BSA-MnO2/Ce6@ZIF-8) with tumor microenvironment controllability. In our system, the hydrophobic photosensitizer chlorin e6 (Ce6) was one-pot incorporated into the matrix of zeolitic imidazolate framework 8 (ZIF-8) to form the Ce6@ZIF-8 compound, which can efficiently keep the Ce6 molecules isolated and avoid them self-aggregate, and the loading rate of Ce6 was high up to 28.3 wt %. The bovine serum albumin (BSA)-MnO2 nanoparticles (NPs) with catalase-like activity were loaded onto the surface of ZIF-8, having the capacity for self-sufficiency of O2 under the circumstance of H2O2 in acid solution, relieving hypoxia in cancer cells and thereby improving the PDT efficiency greatly when irradiated by low power density (230 mW/cm2) 650 nm light. Moreover, the MnO2 NPs react with H2O2 in acid solution to produce Mn2+, granting the system the qualification of a contrast agent for magnetic resonance imaging. Therefore, our nanoplatform would further contribute to the treatment of hypoxic tumors in clinical practice.