Yang Yueqi, Huang Zhangjian, Li Li-Li
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, P. R. China.
Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, P. R. China.
Nanoscale. 2021 Jan 21;13(2):444-459. doi: 10.1039/d0nr07484e.
Nitric oxide (NO), as an endogenous diatomic molecule, plays a key regulatory role in many physiological and pathological processes. This diatomic free radical has been shown to affect different physiological and cellular functions and participates in many regulatory functions ranging from changing the cardiovascular system to regulating neuronal functions. Thus, NO gas therapy as an emerging and promising treatment method has attracted increasing attention in the treatment of various pathological diseases. As is known, the physiological and pathological regulation of NO depends mainly on its location, exposure time and released dosage. However, NO gas lacks effective accumulation and controlled long-term gas releasing capacity at specific sites, resulting in limited therapeutic efficacy and potential side effects. Thus, researchers have developed various NO donors, but eventually found that it is still difficult to control the long-term release of NO. Inspired by the self-assembly properties of nanomaterials, researchers have realized that nanomaterials can be used to support NO donors to form nanomedicine to achieve spatial and temporal controlled release of NO. In this review, according to the history of the medicinal development of NO, we first summarize the chemical design of NO donors, NO prodrugs, and NO-conjugated drugs. Then, NO nanomedicines formed by various nanomaterials and NO donors depending on nanotechnology are highlighted. Finally, the biomedical applications of NO nanomedicine with optimized properties are summarized.
一氧化氮（NO）作为一种内源性双原子分子，在许多生理和病理过程中发挥着关键的调节作用。这种双原子自由基已被证明会影响不同的生理和细胞功能，并参与从改变心血管系统到调节神经元功能等多种调节功能。因此，作为一种新兴且有前景的治疗方法，NO气体疗法在各种病理疾病的治疗中受到了越来越多的关注。众所周知，NO的生理和病理调节主要取决于其位置、暴露时间和释放剂量。然而，NO气体在特定部位缺乏有效的积累和可控的长期气体释放能力，导致治疗效果有限且存在潜在副作用。因此，研究人员开发了各种NO供体，但最终发现仍难以控制NO的长期释放。受纳米材料自组装特性的启发，研究人员意识到可以利用纳米材料来负载NO供体形成纳米药物，以实现NO的时空可控释放。在这篇综述中，根据NO药物开发的历史，我们首先总结了NO供体、NO前药和NO共轭药物的化学设计。然后，重点介绍了由各种纳米材料和NO供体根据纳米技术形成的NO纳米药物。最后，总结了具有优化性能的NO纳米药物的生物医学应用。
