Engineering Smart H ₂ O ₂ Self-Amplifying Nanosystems: From Cascade Mechanisms to Clinical Translation in Tumor Chemodynamic Therapy

This paper reviews recent advances in self-supplying H2O2 nanomaterials for tumor CDT, focusing on innovative strategies to achieve in situ generation of H2O2 through enzymes, nanoenzymes, drugs, metal peroxides, and engineered bacteria. These materials are capable of responsively releasing H2O2 in the TME, overcoming the deficiencies of insufficient endogenous H2O2 concentration, and dramatically enhancing the generation of highly toxic ·OH by Fenton/Fenton-like reaction to achieve precise antitumor therapy. Unlike previous reviews that primarily catalog material types, we introduce conceptual frameworks, including ″cascade reaction engineering″ and ″therapeutic window optimization,″ that provide systematic guidance for rational material design. Despite the challenges of delivery efficiency, long-term safety, and tumor microenvironment adaptability, the self-supplied H2O2 material provides a revolutionary solution to address the challenges of drug resistance and oxygen depletion in tumors through its cascade catalytic, multimodal synergistic, and biodegradable design, which is expected to drive the clinical translation of CDT and expand the paradigm of combination therapy.