Controllable NO release from Cu1.6S nanoparticle decomposition of S-nitrosoglutathiones following photothermal disintegration of polymersomes to elicit cerebral vasodilatory activity

Abstract

Since the discovery of nitric oxide (NO) as a vasodilator, numerous NO therapies have been attempted to remedy disorders related to pathological vasoconstriction such as coronary artery disease. Despite the advances, clinical applications of NO therapies remain limited mainly because of the low stability of molecular NO donors (and NO molecules), and concerns about the increased oxidative stress and reduced arterial pressure associated with the systemic administration of NO. Here we design a photo-responsive polymersome with nitrosothiols and Cu_1.6S nanoparticles in its core and shell, respectively, and demonstrate the photo-triggered release of NO and its vasodilatory activity on zebrafish. Unlike conventional approaches, our design enhances the stability of NO donors and prospectively enables spatiotemporal regulation of NO release, thus minimizing the harmful effects associated with conventional NO therapies. We anticipate that such a strategy will open up new clinical applications of NO and help reveal the complex biological effects of NO in vivo.