心肌缺血再灌注损伤严重威胁人类健康，针对其高效治疗策略的探索势在必行。基因治疗作为一种新兴的治疗手段，有望实现对心肌缺血再灌注损伤的治疗。然而，非特异性、效率低以及不可降解的核酸递送系统严重制约着这一技术的发展。本项目提出基于天然多糖-肽偶合物，构建系列针对心肌缺血再灌注损伤治疗的靶向、可降解核酸递送体系。探索可控的方法将聚阳离子多肽和心脏内皮靶向肽CRPPR引入直链/支链多糖，最终构建系列可共携带干扰炎症细胞粘附因子（ICAM1）合成的siRNA以及表达促血管新生趋化因子（CXCL12）的外源质粒pCXCL12的心脏靶向、可降解核酸递送系统。载体系统靶向心脏后，在目的细胞中释放功能核酸以治疗心肌缺血再灌注损伤。本课题研究有望提高靶向心脏可降解递送载体设计的理论水平，为心肌缺血再灌注损伤治疗的临床前研究提供借鉴。

Myocardial ischemia-reperfusion injury is a serious disease which requires for effective treatment strategies. Gene therapy, as a new therapeutic method, is expected to successfully treat this disease. However, the development of this medical approach is restricted by the non-specific, inefficient and non-degradable nucleic acid delivery system. To solve this problem, this project proposed to construct a series of targeted and degradable nucleic acid delivery systems based on natural polysaccharides-peptide conjugates for the treatment of myocardial ischemia-reperfusion injury. Polycationic polypeptide and cardiac endothelial targeting peptide CRPPR will be introduced into linear/branched polysaccharide as vectors via controlled methods. The final constructed delivery system can effectively target heart. With the degradation in the related cells, the delivery systems can release ICAM1-interfered siRNA (for the inhibition of Inflammatory cell adhesion factors ICAM1) and pCXCL12 (for the expression of angiogenic chemokine CXCL12) for the treatment of myocardial ischemia-reperfusion injury. This study is of great significance not only for the design and potential clinical application of heart-targeted and biodegradable delivery carrier, but also for the development of medical polymers.