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 noninvasive therapeutic method, but CDT still has certain disadvantages such as limited therapeutic efficacy by overexpression of GSH and single treatment mode. In this paper, ZIF-based nanoparticles called Cu2+-SK-GOD@ZIF-90 is constructed for improved chemodynamic therapy and dual starvation therapy (ST). The nanoparticles is destroyed by high levels of ATP in cancer cells, releasing Cu2+, SK and GOD. Under the action of Cu2+ and GSH, Cu+ is generated and catalyzes H2O2 to produce •OH for CDT by Fenton-like reaction. Both the depletion of GSH and the production of H2O2 improves the effect of chemodynamic therapy. Moreover, SK and GOD are used for dual starvation therapy by inhibiting glycolysis and blocking glucose, respectively. The in-vivo experiments have demonstrated that the synergistic treatment of CDT and dual ST by Cu2+-SK-GOD@ZIF-90 can effectively inhibit the growth of tumors and significantly prolong survival of mice, which is better than Cu2+@ZIF-90 and Cu2+-SK@ZIF-90. This synergistic treatment combining CDT and ST offers an effective and safe way to treat cancer.