Modulating nitric oxide-generating activity of zinc oxide by morphology control and surface modification

Abstract

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.