ATP-responsive nanoparticles for improved chemodynamic therapy and dual starvation therapy

Cancer has become a serious threat to human health and the search for a safe and effective treatment method is particularly urgent. Chemodynamic therapy (CDT) is a non-invasive therapeutic method, but CDT still has certain disadvantages such as its limited therapeutic efficacy through overexpression of GSH and single treatment mode. In this paper, ZIF-based nanoparticles called Cu²⁺-SK-GOD@ZIF-90 are constructed for improved chemodynamic therapy and dual starvation therapy (ST). The nanoparticles are destroyed by high levels of ATP in cancer cells, releasing Cu²⁺, shikonin (SK) and glucose oxidase (GOD). Under the action of Cu²⁺ and GSH, Cu⁺ is generated and catalyzes H₂O₂ to produce ˙OH for CDT by a Fenton-like reaction. Both the depletion of GSH and the production of H₂O₂ improve the effect of chemodynamic therapy. Moreover, SK and GOD are used for dual starvation therapy by inhibiting glycolysis and blocking glucose, respectively. <i>In vivo</i> experiments have demonstrated that the synergistic combination of CDT and dual ST via treatment with Cu²⁺-SK-GOD@ZIF-90 can effectively inhibit the growth of tumors and significantly prolong the survival of mice, and is superior to treatment with Cu²⁺@ZIF-90 and Cu²⁺-SK@ZIF-90. This synergistic treatment combining CDT and ST offers an effective and safe way to treat cancer.