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.
Metal–organic frameworks (MOFs) have sparked increasing interest in mimicking the structure and function of natural enzymes. However, their catalytic and therapeutic efficiency are unsatisfactory due to the relatively lower catalytic activity. Herein, inspired by nature, a MOF@COF nanozyme has been designed as a high‐efficiency peroxidase mimic, with the metallic nodes of MOFs as active centres, the hierarchical nanocavities produced by the growth of covalent organic frameworks (COFs) as binding pockets to form tailored pore microenvironment around active sites for enriching and activating substrate molecules, to perform enhanced bacterial inhibition. Furthermore, the pseudopodia‐like surface of the COFs “skin” enabled the system to catch the bacteria effectively for further amplifying the therapeutic efficiency of MOF‐based nanozyme. We believe that the present study will not only facilitate the design of novel nanozymes, but also broaden the biological usage of MOF/COF‐based hybrid materials.
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