A double-gain theranostic nanoplatform based on self-supplying H2O2 nanocomposites for synergistic chemodynamic/gas therapy

Chemodynamic therapy (CDT) based on hydroxyl radicals (center dot OH) to suppress tumor cells is a promising strategy due to its efficacy and safety. Nevertheless, in tumor cells, CDT still faces challenges such as insufficient center dot OH and weak killing effect of tumor cells under physiological conditions due to inadequate amounts of endogenous hydrogen peroxide (H2O2) and heightened glutathione expression. These challenges limit the therapeutic po-tential of CDT. To improve the effects of CDT, combination treatment strategies have been developed. Here, we report a rationally designed nanocomposite (CaO2@Cu-LA) with self-supplying H2O2 ability from calcium peroxide, and nitric oxide (NO) generation ability from L-arginine. NO molecules not only exhibit a strong killing effect, but also have the potential to transfer into the more cytotoxic substance peroxynitrite anion by reacting with reactive oxygen species. The results showed that CaO2@Cu-LA could significantly suppress tumor growth by increasing center dot OH radicals and NO molecules. Taken together, the strategy developed here provides a good application foreground to yield a remarkable synergistic antitumor effect of CDT and NO gas therapy.