Spatiotemporal Nitric Oxide Modulation via Electrochemical Platform to Profile Tumor Cell Response

Nitric oxide (NO) is a gaseous molecule intricately implicated in oncologic processes, encompassing the modulation of angiogenesis and instigating apoptosis. Investigation of the antitumor effects of NO is currently underway, necessitating a detailed understanding of its cellular‐level reactions. Regulating the behavior of radical NO species has been a significant challenge, primarily due to its instability in aqueous environments by rapid O2‐induced degradation. In this study, we devised an electrochemical platform to investigate the cellular responses to reactive gaseous molecules. Our designed platform precisely controlled the NO flux and diffusion rates of NO to tumor cells. COMSOL Multiphysics calculations based on diffusion and reaction kinetics were conducted to simulate the behavior of electrochemically generated NO. We discerned that the effective radius, NO flux, and electrolysis duration are pivotal factors governing cellular response by NO. The dual nature of nitric oxide (NO) in relation to tumor cells necessitates a precise investigation of the critical concentration window of NO. In this manuscript, we introduce Electrochemical System for Conveyance of Radicals to Tumor cells (ESCoRT) a platform that allows precise control of NO generation through electrochemical nitrite reduction. Our study identifies conditions that induce cytotoxicity, offering valuable insights for therapeutic applications.