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.

中文翻译：

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一氧化氮的复兴：从稳定性的提高到内吞作用的增强

在这篇观点文章中，我们回顾了过去40年来对一氧化氮（NO）的探索，并试图了解一氧化氮研究的未来可能方向。从发现NO的生理机制到制造可行的NO输送系统，已经取得了许多惊人的成就。然而，NO作用位点的大部分在细胞内部，并且NO供体的不加选择的分布无疑会导致NO释放和作用位点之间的不匹配。这些错配不仅降低了NO施用的功效，而且还引起了不良的副作用。基于这些论点，我们建议NO的局部生成和细胞内释放与改善载体的稳定性同样重要。还提出了解决该问题的潜在方案。我们希望我们的观点和概念将有助于激发NO应用程序的新想法。