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

Abstract

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 H₂O₂deficiency 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), Cu²⁺, and Mn²⁺were shown to be decomposed and released under weakly acidic conditions in tumor cells. HHTP produces exogenous H₂O₂in the presence of oxygen to increase the H₂O₂content in tumors, Cu²⁺reduces GSH content and generates Cu⁺in the tumor, and Cu⁺and Mn²⁺catalyze H₂O₂to 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 growthin vivo, indicating a good CDT effect.

Keywords: chemodynamic therapy; metal-organic framework; nanocatalyst; tumor targeting.