Bioinspired Construction of a Nanozyme-Based H₂O₂ Homeostasis Disruptor for Intensive Chemodynamic Therapy

The insufficient intracellular H₂O₂ level in tumor cells is closely associated with the limited efficacy of chemodynamic therapy (CDT). Despite tremendous efforts, engineering CDT agents with a straightforward and secure H₂O₂ supplying ability remains a great challenge. Inspired by the balance of H₂O₂ generation and elimination in cancer cells, herein, a nanozyme-based H₂O₂ homeostasis disruptor is fabricated to elevate the intracellular H₂O₂ level through facilitating H₂O₂ production and restraining H₂O₂ elimination for enhanced CDT. In the formulation, the disruptor with superoxide dismutase-mimicking activity can convert O₂^•- to H₂O₂, promoting the production of H₂O₂. Simultaneously, the suppression of catalase activity and depletion of glutathione by the disruptor weaken the transformation of H₂O₂ to H₂O. Thus, the well-defined system could perturb the H₂O₂ balance and give rise to the accumulation of H₂O₂ in cancer cells. The raised H₂O₂ level would ultimately amplify the Fenton-like reaction-based CDT efficiency. Our work not only paves a way to engineer alternative CDT agents with a H₂O₂ supplying ability for intensive CDT but also provides new insights into the construction of bioinspired materials.