Department of Chemistry, Pohang University of Science and Technology, Pohang 790-784, Korea.
Bioconjug Chem. 2011 Jun 15;22(6):1031-8. doi: 10.1021/bc100405c. Epub 2011 May 26.
In recent years, numerous research activities have been devoted to the controlled release of nitric oxide (NO) due to its potential as a restenosis inhibitor which inhibits the proliferation of vascular smooth muscle cells, the apoptosis of vascular endothelial cells, and aggregation of platelets. This work has demonstrated the development of a novel NO-conjugated gel system comprising of thermosensitive Pluronic F127, branched polyethylenimine (BPEI), and diazeniumdiolates (NONOates). Synthesis of conjugated Pluronic-BPEI-NONOates involved coupling of activated F127 to BPEI followed by the installation of NONOates at the secondary amine sites of branched PEI backbone under high pressure. NO-conjugated gel system, F127-BPEI-NONOates, reduced the initial burst of NO release and prolonged NO release. Furthermore, F127-BPEI-NONOates polymer coated on cell culture dish displayed much higher increase of endothelial cell proliferation and reduction of smooth muscle cell proliferation than that exhibited by non-NO releasing control. Such an NO-releasing device can operate locally and has a great potential in several biomedical applications due to high biocompatibility imparted by the conjugated F127.
近年来，由于一氧化氮（NO）作为抑制血管平滑肌细胞增殖、血管内皮细胞凋亡和血小板聚集的再狭窄抑制剂的潜力，人们开展了大量关于其控制释放的研究活动。这项工作已经证明了一种新型 NO 结合凝胶系统的开发，该系统由温敏性 Pluronic F127、支化聚乙烯亚胺（BPEI）和重氮二羧酸酯（NONOates）组成。共轭 Pluronic-BPEI-NONOates 的合成涉及将活化的 F127 与 BPEI 偶联，然后在高压下将 NONOates 安装在支化 PEI 主链的二级胺位点上。NO 结合凝胶系统 F127-BPEI-NONOates 减少了 NO 释放的初始突释，并延长了 NO 的释放。此外，涂覆在细胞培养皿上的 F127-BPEI-NONOates 聚合物显示出比非 NO 释放对照物更高的内皮细胞增殖增加和平滑肌细胞增殖减少。由于结合的 F127 赋予的高生物相容性，这种 NO 释放装置可以局部操作，并且在几种生物医学应用中具有很大的潜力。
