基于化学生物学“凸凹互补”原理构建靶向一氧化氮递送系统用于缺血性疾病治疗

一氧化氮作为一类重要的信号分子，在血管损伤修复的多个关键过程中发挥关键作用。但是，一氧化氮分子半衰期短、传输距离有限，由于缺乏有效的递送手段，严重限制了其临床应用。本项目中，我们利用化学生物学“凸凹互补”原理构建靶向一氧化氮递送系统，将一氧化氮精准递送至病损组织，从而有效解决非特异性释放引发的副作用等问题。我们将采用近红外成像技术示踪一氧化氮化合物在体内的递送行为。进一步，利用不同动物模型系统考察靶向一氧化氮递送体系对缺血性疾病（下肢缺血、肾缺血等）的治疗效果，深入研究一氧化氮信号分子在血管形成、炎症反应和组织修复再生等多个关键过程中的重要作用和相关机制。

Nitric oxide (NO), as a key signalling molecule, plays a vital role in the multiple processes of vascular repair and regeneration. NO-based therapies are limited clinically due to lack of effective strategies for precisely delivering NO to a specific site that is mainly ascribed to the limited transportation distance and short half-life. In the present project, we will develop a novel NO delivery system using a “bump-and-hole” strategy. Targeted delivery of NO could markedly abolish side effects due to the systemic release of NO. Precise delivery to targeted tissues will be clearly demonstrated by an in vivo near-infrared (NIR) imaging assay. The therapeutic potential for various ischaemic diseases will be evaluated in both rat hindlimb ischaemia and mouse acute kidney injury (AKI) models. Furthermore, the effect of nitric oxide on the angiogenesis, inflammation modulation, as well as tissue repair and regeneration will be systematically investigated.