The renaissance of nitric oxide: from improvement of stability to enhancement of endocytosis

Abstract

In this perspective article, we have reviewed the exploration of nitric oxide (NO) over the past 40 years and tried to catch a glimpse of the possible future direction of NO research. A lot of astounding achievements have already been made, from the discovery of the physiological mechanism of NO to the fabrication of a feasible NO delivery system. However, a large portion of NO action sites are inside cells, and indiscriminate distribution of NO donors would undoubtedly bring about a mismatch between the NO release and action sites. These mispairings not only reduce the efficacy of NO applications, but also cause undesirable side effects. Based on these arguments, we propose that the local generation and intracellular release of NO is no less vital than improving the stability of the carriers. Potential solutions to this problem have also been put forward. We hope our views and concepts will prove helpful to inspire new ideas for NO applications.