H₂O₂‐Generating Advanced Nanomaterials for Cancer Treatment

Abstract

Abstract 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 H 2 O 2 in tumor cells through both endogenous and exogenous mechanisms. The generated H 2 O 2 serves as a precursor for toxic ROS, such as • OH and 1 O 2 , via chemodynamic and photodynamic therapy, respectively, leading to apoptosis, necrosis, and ferroptosis. Strategies to boost H 2 O 2 levels include direct delivery of exogenous H 2 O 2 and amplifying endogenous H 2 O 2 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 H 2 O 2 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 H 2 O 2 ‐generating nanoplatforms, emphasizing their capacity to treat various cancers.