Synergizing Pyroelectric Catalysis and Enzyme Catalysis: Establishing a Reciprocal and Synergistic Model to Enhance Anti-Tumor Activity.

Nanozyme activity is greatly weakened by the microenvironment and multidrug resistance of tumor cells. Hence, a bi-catalytic nanoplatform, which promotes the anti-tumor activity through "charging empowerment" and "mutual complementation" processes involved in enzymatic and pyroelectric catalysis, by loading ultra-small nanoparticles (USNPs) of pyroelectric ZnSnO onto MXene nanozyme (VCT nanosheets), is developed. Here, the VCT nanosheets exhibit enhanced peroxidase activity by reacting V with HO to generate toxic ·OH, accelerated by the near-infrared (NIR) light mediated heat effect. The resulting V is then converted to V by oxidizing endogenous glutathione (GSH), realizing an enzyme-catalyzed cycle. However, the cycle will lose its persistence once GSH is insufficient; nevertheless, the pyroelectric charges generated by ZnSnO USNPs continuously support the V/V conversion and ensure nanoenzyme durability. Moreover, the hyperthermia arising from the VCT nanosheets by NIR irradiation results in an ideal local temperature gradient for the ZnSnO USNPs, giving rise to an excellent pyroelectric catalytic effect by promoting band bending. Furthermore, polarized charges increase the tumor cell membrane permeability and facilitate nanodrug accumulation, thereby resolving the multidrug resistance issue. Thus, the combination of pyroelectric and enzyme catalysis together with the photothermal effect solves the dilemma of nanozymes and improves the antitumor efficiency.