Bridging OER Electrocatalysis and Tumor Therapy: Utilizing Piezoelectric‐Hole‐Induced OER Electrocatalysis for Direct Oxygen Generation to Address Hypoxia

In addressing the challenge of hypoxia within the tumor microenvironment (TME), a significant obstacle to effective cancer therapy, this research introduces a pioneering nanozyme engineered to utilize water and oxygen as reactants. Utilizing ultrasonic piezoelectricity, this nanozyme converts these substrates into oxygen (O2) and reactive oxygen species, thereby amplifying oxidative stress without relying on endogenous H2O2. This approach involves the strategic engineering of porous ZnSnOv:Mn nanosheets (named MZSO NSs), which are distinguished by oxygen‐rich vacancies and enhanced piezoelectric properties. This breakthrough represents the initial attempt to merge catalytic activities akin to catalase (CAT) with the electrocatalytic oxygen evolution reaction (OER), confirmed through both enzymatic reactions and electrochemical voltammetric analysis. The predominant mechanism of ultrasound‐augmented oxygen generation in MZSO is identified as piezoelectric hole‐induced OER. Supporting theoretical analyses clarify the synergistic impact of oxygen vacancies and Mn doping on the dynamics of carriers and the OER process, leading to a notable increase in catalytic efficiency. These findings highlight the potential of piezoelectric‐enhanced OER electrocatalysts to alleviate hypoxia in the TME, providing novel insights into the development of piezoelectric acoustic sensitizers for the treatment of cancer. Synthesized ZnSnOv:Mn NSs enhance carrier utilization and ROS production through doping engineering and piezoelectric effects. Crucially, the relationship between catalase (CAT) and oxygen evolution reaction (OER) reactions is clarified, using piezoelectric‐induced OER to generate O2 in acidic environments. This method minimizes dependence on endogenous H2O2 in tumor therapies and effectively addresses O2 depletion in TME and SDT.