A Highly Biocompatible Polyoxotungstate with Fenton-like Reaction Activity for Potent Chemodynamic Therapy of Tumors

Abstract

Integrating Fenton chemistry and nanomedicine into cancer therapy has significantly promoted the development of chemodynamic therapy (CDT). Nanoscale polyoxometalates (POMs), with their reversible redox properties, exhibit promising potential in developing outstanding CDT drugs by exploring their Fenton-like catalytic reactivity in tumor environments. However, such research is still in its infancy due to the challenges of acquiring POMs that are both easily prepared and possess ideal therapeutic effects, physiological solubility, biocompatibility and safety. In this work, we report the synthesis of a new crystalline antimonotungstate {Dy₂Sb₂W₇O₂₃(OH)(DMF)₂(SbW₉O₃₃)₂} (1, DMF=N, N-dimethylformamide) with gram-scale high yield via a facile “one-pot” solvothermal reaction. 1 exhibits not only a soluble and water-stable POM nanocluster, but also excellent catalytic activity for hydroxyl radical-generating Fenton-like reactions. Further biomedical studies reveal that 1 can trigger cell apoptosis and promote lipid peroxidation, exhibiting high cytotoxicity and selectivity towards B16-F10 mouse melanoma cancer cells with an IC₅₀ value of 4.75 μM. Especially, 1 can inhibit melanoma growth in vivo with favorable biosafety, achieving a 5.2-fold reduction in tumor volume and a weight loss of 76.0 % at the dose of 70 μg/kg. This research not only demonstrates the immense potential of antimonotungstates in CDT drug development for the first time but also provides new insights and directions for the development of novel anticancer drugs.