Rational Design of Guanidinium-Based Bio-MCOF as a Multifunctional Nanocatalyst in Tumor Cells for Enhanced Chemodynamic Therapy

Chemodynamic therapy (CDT) has emerged as a promising approach to cancer treatment, which can break the intracellular redox state balance and result in severe oxidative damage to biomolecules and organelles with the advantages of being less dependent on external stimulation, having deep tissue-healing abilities, and being resistant to drug resistance. There is considerable interest in developing CDT drugs with high efficiency and low toxicity. In this study, a new guanidinium-based biological metal covalent organic framework (Bio-MCOF), GZHMU-1@Mo, is rationally designed and synthesized as a multifunctional nanocatalyst in tumor cells for enhanced CDT. The DFT calculation and experimental results showed that due to the ability of MoO₄^2- ion to promote electron transfer and increase the redox active site, Cu₃ clusters and MoO₄^2- ions in GZHMU-1@Mo can synergistically catalyze the production of reactive oxygen species (ROS) from oxygen and H₂O₂ in tumor cells, as well as degrade intracellular reducing substances, GSH and NADH, so as to disrupt the redox balance in tumor cells. Moreover, GZHMU-1@Mo exhibits a potent killing effect on tumor cells under both normal oxygen and anaerobic conditions. Further in vitro and in vivo antiproliferation studies revealed that the GZHMU-1@Mo nanoagent displays a remarkable antiproliferation effect and effectively inhibits tumor growth. Taken together, our study provides an insightful reference benchmark for the rational design of Bio-MCOF-based nanoagents with efficient CDT.