H₂O₂‐Generating Advanced Nanomaterials for Cancer Treatment

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 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.