Zinc oxide (ZnO) has emerged as a promising material for nitric oxide (NO) delivery owing to its intrinsic enzyme-mimicking activities to catalyze NO prodrugs S-nitrosoglutathione (GSNO) and β-gal-NONOate for NO generation. The catalytic performance of enzyme mimics is strongly dependent on their size, shape, and surface chemistry; however, no studies have evaluated the influence of the aforementioned factors on the NO-generating activity of ZnO. Understanding these factors will provide an opportunity to tune NO generation profiles to accommodate diverse biomedical applications. In this paper, for the first time, we demonstrate that the activity of ZnO towards catalytic NO generation is shape-dependent, resulting from the different crystal growth directions of these particles. We modified the surfaces of ZnO particles with zeolitic imidazolate framework (ZIF-8) by in situ synthesis and observed that ZnO/ZIF-8 retained 60% of its NO-generating potency. The newly formed ZnO/ZIF-8 particles were shown to catalytically decompose both endogenous (GSNO) and exogenous (β-gal-NONOate and S-nitroso-N-acetylpenicillamine (SNAP)) prodrugs to generate NO at physiological conditions. In addition, we design the first platform that combines NO-generating and superoxide radical scavenging properties by encapsulating a natural enzyme, superoxidase dismutase (SOD), into ZnO/ZIF-8 particles, which holds great promise towards combinatorial therapy.

氧化锌 (ZnO) 由于其固有的酶模拟活性来催化 NO 前药S-亚硝基谷胱甘肽 (GSNO) 和β-gal-NONOate 用于 NO 生成。酶模拟物的催化性能很大程度上取决于它们的大小、形状和表面化学性质；然而，没有研究评估上述因素对 ZnO 生成 NO 活性的影响。了解这些因素将为调整 NO 生成谱以适应不同的生物医学应用提供机会。在本文中，我们首次证明了 ZnO 对催化 NO 生成的活性是形状相关的，这是由于这些颗粒的不同晶体生长方向造成的。我们通过原位合成用沸石咪唑酯骨架 (ZIF-8) 修饰了 ZnO 颗粒的表面，并观察到 ​​ZnO/ZIF-8 保留了 60% 的 NO 生成能力。β -gal-NONOate 和S-亚硝基-N-乙酰青霉胺 (SNAP)) 前药在生理条件下产生 NO。此外，我们设计了第一个平台，通过将天然酶超氧化物酶歧化酶 (SOD) 封装到 ZnO/ZIF-8 颗粒中，将产生 NO 和清除超氧化物自由基的特性相结合，这对组合疗法具有很大的前景。