A Mn-porphyrinic metal–organic framework immobilizing glucose oxidase for combined photodynamic/chemodynamic/starvation therapy
The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) in tumor treatment has attracted considerable attention. However, tumor hypoxia and glutathione (GSH) overproduction in the tumor tissue restricted the progress of their applications. Herein, a Mn-porphyrinic metal–organic framework (Mn-TCPP) was constructed by the one-pot method and further used for immobilizing glucose oxidase (GOx) to obtain GOx@Mn-TCPP. GOx would rapidly exhaust endogenous glucose into hydrogen peroxide (H 2 O 2 ) and gluconic acid, thus shutting off the energy supply of tumor cells for starvation treatment. Mn-TCPP catalyzed H 2 O 2 to produce oxygen, regulating the hypoxic tumor microenvironment and in turn improving 1 O 2 generation under laser irradiation. Interestingly, Mn-TCPP can reduce reactive oxygen species consumption owing to the redox reaction between Mn 3+ and GSH, thus greatly enhancing PDT. Furthermore, benefiting from GOx-mediated starvation therapy, Mn 2+ produced by Mn 3+ reduction can react with sufficient intracellular H 2 O 2 to generate ·OH with high cytotoxicity through a Fenton-like reaction. After treatment by GOx@Mn-TCPP under laser irradiation in vitro, the cell viability of 4T1 and A549 tumor cells reached to 20%, reflecting GOx@Mn-TCPP could give full play to the advantages of PDT/CDT/starvation therapy. The results in vivo demonstrated that GOx@Mn-TCPP mediated synergistic cascade therapy could significantly inhibit tumor growth and improve the therapeutic effect.
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