Multifunctional Zeolitic\nImidazolate Framework Nanocomposites\nas Fenton Catalysts for Synergistic Chemodynamic-Photothermal-Chemo\nTherapy

Abstract

Multifunctional nanomaterials have become a promising\nnanoplatform\nfor anticancer treatment with tumor specific activation. Here, a cancer\ncell-activated nanocomposite Cu/ZIF-8@MPN@DOX@F127 (CZMDF) was constructed\nwith a metal phenolic network (MPN)-modified Cu/ZIF-8 and loaded with\ndoxorubicin (DOX). CZMDF was degraded to release tannic acid (TA),\nFe³⁺, Cu²⁺, and DOX in cancer cells. Benefiting\nfrom the reducibility of TA, Fe³⁺ was converted to Fe²⁺, which could react with endogenous H₂O₂ to produce a highly toxic hydroxyl radical (^•OH)\nby the Fenton reaction. The Fenton reaction-mediated chemodynamic\ntherapy (CDT) was promoted by the accelerated Fe³⁺/Fe²⁺ conversion, which was also enhanced with a Cu²⁺-based Fenton-like reaction. In addition, endogenous glutathione\n(GSH) could reduce Fe³⁺ and Cu²⁺ to Fe²⁺ and Cu⁺, which led to further enhancement of CDT performance.\nDOX acted as a traditional drug to realize chemotherapy. Furthermore,\nthe heat from MPN after near-infrared irradiation (NIR) could be applied\nto realize photothermal therapy (PTT). The multifunctional nanocomposite\nwas designed to achieve synergistic tumor treatment with CDT/chemotherapy/PTT.\nIn vitro experiments showed that the CZMDF caused about 70% of cell\napoptosis, and the tumor growth in mice was also inhibited in vivo\nstudy. This multifunctional nanomaterial enriches the nanocatalyst\ntypes for synergistic tumor therapy, providing a nanoplatform for\npotential clinical transitions.