A Nanoreactor Based on Metal–Organic Frameworks With Triple Synergistic Therapy for Hepatocellular Carcinoma

Abstract The transformation of monotherapy into multimodal combined targeted therapy to fully exploit synergistic efficacy is of increasing interest in tumor treatment. In this work, a novel nanodrug‐carrying platform based on iron‐based MOFs, which is loaded with doxorubicin hydrochloride (DOX), dihydroartemisinin (DHA), and glucose oxidase (GO x ), and concurrently covalently linked to the photosensitizer 5,10,15,20‐tetrakis(4‐carboxyphenyl)porphyrin (TCPP) in polydopamine (PDA)‐encapsulated MIL‐101(Fe) (denoted as MIL‐101(Fe)‐DOX‐DHA@TCPP/GOx@PDA, MDDTG@P), is successfully developed. Upon entering the tumor microenvironment, MDDTG@P catalyzes the hydrogen peroxide (H 2 O 2 ) into hydroxyl radicals (·OH) and depletes glutathione (GSH); thus, exerting the role of chemodynamic therapy (CDT). The reduced Fe 2+ can also activate DHA, further expanding CDT and promoting tumor cell apoptosis. The introduced GO x will rapidly consume glucose and oxygen (O 2 ) in the tumor; while, replenishing H 2 O 2 for Fenton reaction, starving the cancer cells; and thus, realizing starvation and chemodynamic therapy. In addition, the covalent linkage of TCPP endows MDDTG@P with good photodynamic therapeutic (PDT) properties. Therefore, this study develops a nanocarrier platform for triple synergistic chemodynamic/photodynamic/starvation therapy, which has promising applications in the efficient treatment of tumors.