Tumor-Targeted Cascade Nanoreactor Based on Metal-Organic Frameworks for Synergistic Ferroptosis-Starvation Anticancer Therapy.

Abstract

Although ferroptosis therapy has been proven to be a promising strategy for cancer treatment, its efficacy still might be limited by insufficient H₂O₂ supply in tumor tissue. Herein, we designed a cancer cell membrane-cloaked cascade nanoreactor based on ferric metal-organic frameworks (MOF) and glucose oxidase (GOx) decoration for synergistic ferroptosis-starvation anticancer therapy. The GOx can catalyze glucose to generate sufficient H₂O₂ for ferroptosis therapy, and the glucose consumption caused by GOx can be utilized as another attractive cancer treatment strategy called starvation therapy. When the nanoreactor reached tumor sites, high concentration of GSH reduced Fe³⁺ to trigger structure collapse of MOF and release Fe²⁺ and GOx catalyzed the oxidation of glucose to generate H₂O₂. Then Fenton reaction happened between H₂O₂ and Fe²⁺ to produce hydroxyl radicals (^•OH) and promoted ferroptosis therapy. With these cascade reactions, the synergistic ferroptosis-starvation anticancer therapy was realized. Furthermore, the cancer cell membrane endows the nanoreactor homologous targeting and immune escaping ability, which facilitated the nanoreactor to accumulate into tumor site with high efficiency. The nanoreactor exhibits high efficiency for tumor suppression with the <i>in situ</i> consumed and produced compounds, which can promote the development of precise cooperative cancer therapy with spatiotemporal controllability.