MOF-Supported Gold Nanozyme with Glutathione Consumption and Oxidative Stress Amplification against Cancer Cells

Abstract

Nanozymes exploit the acidic pH and abundant biomarkers in the tumor microenvironment (TME) to selectively target tumors and enhance chemodynamic therapy (CDT) via a cascade of enzymatic reactions that generate cytotoxic free radicals, thereby improving the therapeutic efficacy. In this study, we engineered a MOF-supported gold nanozyme (Au@ABI-ZIF-8). By depleting the abundant glutathione (GSH) in TME, the resulting Au@ABI-ZIF-8_G exhibited outstanding superoxide dismutase-like and glucose oxidase-like activities, capable of continuously converting endogenous superoxide anion (^•O₂^–) and oxygen into H₂O₂. Meanwhile, in the acidic TME, the peroxide-like activity of Au@ABI-ZIF-8_G converted H₂O₂ into more toxic ^•OH, demonstrating a stronger killing effect on cancer cells, as comprehensively validated using HeLa and SiHA cell lines. Therefore, the cascade enzymatic reaction of Au@ABI-ZIF-8 depleted GSH and glucose, achieved more toxic ^•OH, amplified oxidative stress in the TME, and ultimately improved the CDT efficacy against cancer cells. This approach could potentially be extended to design other MOF-supported AuNCs with coligands and multienzymes, offering a promising direction for the development of novel nanozymes and expanding their applications in the field of nanobiomedicine.