A Versatile Nanoplatform Based on Metal‐Phenolic Networks Inhibiting Tumor Growth and Metastasis by Combined Starvation/Chemodynamic/Immunotherapy

Abstract Although much progress has been made by multifunctional nanoplatforms in the treatment of cancer, several defects of existing nanoplatforms, such as tedious preparation, poor biocompatibility, and failure to activate the immune system, have limited their clinical applications. Herein, a versatile nanosystem of folic acid‐modified metal‐phenolic networks (MPNs) loaded with GOx and CHA (F‐MGC) is fabricated by the easy self‐assembly of MPNs, during which glucose oxidase (GOx) and chlorogenic acid (CHA) are concurrently loaded. The resulting nanosystem, having a folic acid‐modified surface and inherent acid sensitivity, shows versatility in being able to target tumors and release active ingredients in the weakly acidic tumor microenvironment (TME). Based on the catalysis of GOx and Fe³⁺, the cascade reaction aroused by F‐MGC efficiently consumes glucose in the TME and produces abundant cytotoxic hydroxyl radicals, thereby causing the starving and chemodynamic death of cancer cells. In addition, CHA can reshape M2 tumor‐associated macrophages (TAMs) into the M1 type, so as to change the immunosuppressive state of TME. The immunogenic cell death (ICD) that occurs from the starvation and chemodynamic therapy, in conjunction with the CHA‐induced TAMs polarization, further activates the immune system. Overall, the easily prepared nanoplatform has excellent biocompatibility and effectively inhibits tumor growth and metastasis.