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

The insufficient intracellular HO 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 HO supplying ability remains a great challenge. Inspired by the balance of HO generation and elimination in cancer cells, herein, a nanozyme-based HO homeostasis disruptor is fabricated to elevate the intracellular HO level through facilitating HO production and restraining HO elimination for enhanced CDT. In the formulation, the disruptor with superoxide dismutase-mimicking activity can convert O to HO, promoting the production of HO. Simultaneously, the suppression of catalase activity and depletion of glutathione by the disruptor weaken the transformation of HO to HO. Thus, the well-defined system could perturb the HO balance and give rise to the accumulation of HO in cancer cells. The raised HO 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 HO supplying ability for intensive CDT but also provides new insights into the construction of bioinspired materials.