Multifunctional Zeolitic Imidazolate Framework Nanocomposites as Fenton Catalysts for Synergistic Chemodynamic-Photothermal-Chemo Therapy

Multifunctional nanomaterials have become a promising nanoplatform for anticancer treatment with tumor specific activation. Here, a cancer cell-activated nanocomposite Cu/ZIF-8@MPN@DOX@F127 (CZMDF) was constructed with a metal phenolic network (MPN)-modified Cu/ZIF-8 and loaded with doxorubicin (DOX). CZMDF was degraded to release tannic acid (TA), Fe3+, Cu2+, and DOX in cancer cells. Benefiting from the reducibility of TA, Fe3+ was converted to Fe2+, which could react with endogenous H2O2 to produce a highly toxic hydroxyl radical (•OH) by the Fenton reaction. The Fenton reaction-mediated chemodynamic therapy (CDT) was promoted by the accelerated Fe3+/Fe2+ conversion, which was also enhanced with a Cu2+-based Fenton-like reaction. In addition, endogenous glutathione (GSH) could reduce Fe3+ and Cu2+ to Fe2+ and Cu+, which led to further enhancement of CDT performance. DOX acted as a traditional drug to realize chemotherapy. Furthermore, the heat from MPN after near-infrared irradiation (NIR) could be applied to realize photothermal therapy (PTT). The multifunctional nanocomposite was designed to achieve synergistic tumor treatment with CDT/chemotherapy/PTT. In vitro experiments showed that the CZMDF caused about 70% of cell apoptosis, and the tumor growth in mice was also inhibited in vivo study. This multifunctional nanomaterial enriches the nanocatalyst types for synergistic tumor therapy, providing a nanoplatform for potential clinical transitions.