靶向动脉粥样硬化可示踪的抗自由基和抗炎损伤聚阳离子核酸递送系统研究

自由基损伤和炎性损伤是促进动脉粥样硬化(AS)病情进展最为重要的病理机制。课题申请者前期研究表明利用聚阳离子核酸载体负载靶基因的血管支架具有改善支架后血管再狭窄的功能。本研究以前期工作为基础，以甲基丙烯酸缩水甘油酯、氨基TEMPO、乙醇胺为基本反应物，通过可控聚合、氨基与环氧的开环反应和酰胺化后修饰引入靶向多肽，构建具有核磁成像功能可活体示踪、清除自由基的靶向聚阳离子核酸递送载体。利用该核酸递送载体修饰负载能够对抗AS病理过程、减轻AS动脉损伤的抗炎蛋白IL-10、ACE2、AnxA1质粒，将其递送至AS局部病变组织。最终构建出可以通过抗炎和清除自由基联合机制靶向AS病变部位、可以活体示踪的新型多功能聚阳离子核酸递送体系。预期研究结果对于提高多功能基因递送载体的理论创新水平和实际探索应用都有很大的学术价值，同时为动脉粥样硬化的治疗提供新的思路，对推动医用材料学科的发展也具有一定的意义。

Free radical injury and inflammatory injury are the most important pathological mechanisms of atherosclerosis (AS), which accelerate the progression of atherosclerosis. Preliminary study showed that the vessel stent loaded with target gene by polycationic acid delivery vector could improve vessel restenosis after stent. This study is based on previous research work,glycidyl methacrylate, amino TEMPO, and ethanolamine were used as basic reactive substances. Targeted polypeptides, which were made through controllable polymerization, ring-opening reaction of amino groups and epoxy, and modification after amidation, were used to construct a targeted polycationic nucleic acid delivery vector with MRI imaging function for in vivo tracking and scavenging free radicals against oxidative damage. Using this nucleic acid delivery vector to modify the load can counteract the pathological process of AS and reduce AS arterial damage associated anti-inflammatory protein IL-10, ACE2, AnxA1 functional gene plasmids delivered to AS local lesion tissue. Eventually a new multifunctional polycationic nucleic acid delivery system was constructed, which can be applied to AS treatment through the combined mechanisms of anti-inflammatory and anti-free radicals and be traced in vivo. The expected results have great academic value for improving the theoretical innovation level and exploring practical application of multifunctional gene delivery vectors. And it has widely prospect in clinical practice and can provide a new idea for the treatment of AS. In addition, it has important significance for further promoting the development of medical polymer science.