Hyaluronic acid modified Cu/Mn-doped metal-organic framework nanocatalyst for chemodynamic therapy

Chemodynamic therapy (CDT) is a new method for cancer treatment that produces highly toxic reactive oxygen species (ROS) in the tumor microenvironment to induce cancer cell apoptosis or necrosis. However, the therapeutic effect of CDT is often hindered by intracellular HO deficiency and the activity of antioxidants such as glutathione (GSH). In this study, a nano-catalyst HCM was developed using a self-assembled Cu/Mn-doped metal-organic framework, and its surface was modified with hyaluronic acid to construct a tumor-targeting CDT therapeutic agent with improved the efficiency and specificity. Three substances HHTP (2, 3, 6, 7, 10, 11-hexahydroxybenzophenanthrene), Cu, and Mn were shown to be decomposed and released under weakly acidic conditions in tumor cells. HHTP produces exogenous HO in the presence of oxygen to increase the HO content in tumors, Cu reduces GSH content and generates Cu in the tumor, and Cu and Mn catalyze HO to produce ∙OH in a Fenton-like reaction. Together, these three factors change the tumor microenvironment and improve the efficiency of ROS production. HCM showed selective and efficient cytotoxicity to cancer cells, and could effectively inhibit tumor growth in vivo, indicating a good CDT effect.