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

[Display omitted] • ● The CaO 2 @Cu-LA nanocomposite exhibits a crystal structure of CaO 2 and a coordination structure between metal and amino acid. • ● The CaO 2 @Cu-LA possesses the capability of self-generating H 2 O 2. • ● The CaO 2 @Cu-LA generates •OH, O 2 –•, and NO while consuming GSH under acidic conditions. • ● The CaO 2 @Cu-LA interferes with mitochondrial energy production and disrupts the structure of DNA double strands. • ● The CaO 2 @Cu-LA exhibits significant efficacy in eradicating tumor cells both in vitro and in vivo. Chemodynamic therapy (CDT) based on hydroxyl radicals (•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 •OH and weak killing effect of tumor cells under physiological conditions due to inadequate amounts of endogenous hydrogen peroxide (H 2 O 2) and heightened glutathione expression. These challenges limit the therapeutic potential of CDT. To improve the effects of CDT, combination treatment strategies have been developed. Here, we report a rationally designed nanocomposite (CaO 2 @Cu-LA) with self-supplying H 2 O 2 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 CaO 2 @Cu-LA could significantly suppress tumor growth by increasing •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. [ABSTRACT FROM AUTHOR]