Dehydrogenase-like stacked MoS2 nanozymes for cancer treatment through disrupting tricarboxylic acid cycle

Abstract

Metabolic reprogramming is a crucial driver of tumorigenesis, providing the energy and cellular environment required for the uncontrolled growth and proliferation of tumor cells. Disturbing tumor metabolic pathways, such as targeting the tricarboxylic acid (TCA) cycle, represents a promising and innovative approach to cancer therapy. In this study, we engineer stacked molybdenum disulfide nanosheets (MSs) nanozymes with a unique "potato tower" morphology. These nanozymes exhibit distinctive dehydrogenase-like catalytic activity, enabling the conversion of α-ketoglutarate (α-KG) to succinic acid, thereby regulating the TCA cycle in tumor cells and inducing significant mitochondrial damage. In in vivo treatment of malignant triple negative breast cancer, the MSs achieved a remarkable 77% tumor inhibition rate. This study highlights the potential of the stacked MoS2 nanosheets as a promising therapeutic agent, and presents a novel strategy for tumor treatment by targeting metabolic pathways.