H2O2-Generating Advanced Nanomaterials for Cancer Treatment

Tumor cells exploit abnormal redox homeostasis and the pro-tumorigenic effect of reactive oxygen species (ROS) to enhance their survival and progression. However, excessively high levels of ROS can exceed the oxidative stress threshold of tumor cells, inducing cell death. This can occur by selectively elevating the concentration of H2O2 in tumor cells through both endogenous and exogenous mechanisms. The generated H2O2 serves as a precursor for toxic ROS, such as ?OH and 1O2, via chemodynamic and photodynamic therapy, respectively, leading to apoptosis, necrosis, and ferroptosis. Strategies to boost H2O2 levels include direct delivery of exogenous H2O2 and amplifying endogenous H2O2 generation by inhibiting antioxidant enzymes, leveraging glucose oxidase, employing photocatalytic therapy (PCT), and utilizing metal peroxides. Among them, metal peroxides have displayed remarkable performance due to their excellent potential to elevate H2O2 concentration within tumor cells while simultaneously normalizing the acidic and hypoxic conditions of the tumor microenvironment (TME). Moreover, these nanostructures enhance tumor sensitivity to complementary treatments, like chemotherapy. This review summarizes advanced perspectives in the design, synthesis, and comparative analysis of H2O2-generating nanoplatforms, emphasizing their capacity to treat various cancers.