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

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 in situ consumed and produced compounds, which can promote the development of precise cooperative cancer therapy with spatiotemporal controllability.