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 H 2 O 2 nanomaterials for tumor CDT, focusing on innovative strategies to achieve in situ generation of H 2 O 2 through enzymes, nanoenzymes, drugs, metal peroxides, and engineered bacteria. These materials are capable of responsively releasing H 2 O 2 in the TME, overcoming the deficiencies of insufficient endogenous H 2 O 2 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 H 2 O 2 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.