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

Abstract

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. In vivo 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.