调节线粒体的生理功能是心肌缺血/再灌注(I/R)损伤新的治疗策略，目前许多药物很难到达缺血心肌细胞线粒体，导致疗效不理想。本课题构建载葛根素（模型药物）的序级靶向纳米胶束：基于PEG-PE的EPR效应，先将载药胶束蓄积于梗死早期的缺血心肌；再以MMPs肽靶向结合缺血心肌部位的MMPs，增加纳米胶束的滞留效应；并借助于TPP阳离子的电荷效应，介导药物载体进入线粒体，将葛根素逐步靶向到线粒体，实现精准化给药。为验证该载药系统的序级靶向功能，课题组采用多种技术手段，从“整体动物-心脏-心肌细胞-线粒体”四个层面探索纳米胶束的靶向性，同时研究该胶束克服生物膜屏障的“逃避网状内皮系统吞噬”和“溶酶体逃逸”功能；通过调节线粒体功能、减少心肌I/R损伤试验，从细胞和动物水平上评价葛根素纳米胶束的线粒体靶向作用。本项目有望实现药物的缺血心肌细胞线粒体靶向传输，为高效的心肌I/R损伤精确治疗奠定研究基础。

Regulating the physiological function of myocardial cell mitochondria is a new therapeutic strategy for myocardial ischemia-reperfusion injury, At present many drugs are difficult to reach the ischemic myocardial cell mitochondria, leading to unsatisfactory curative effect. The research will establish puerarin(model drug) loaded ordinal targeted nano-micelles: Based on the EPR effect of PEG-PE, drug micelles could accumulate in the ischemic myocardial tissue at the early infarction, MMPs peptide owns an obvious target affinity toward MMPs in the ischemic myocardium, which may enhance the retention effect of nano-micelles, finally the drug carriers can get into the mitochondria mediated by the charge effect of TPP cation, puerarin can be gradually targeted to mitochondria, realizing the accurate delivery of drugs. In order to verify the ordinal targeting function of this drug delivery system, the targeting of this nano-micelles will be studied at the four level of "whole animal-heart-myocardial cell-mitochondria" by a variety of technical means. The"phagocytic effect of the reticuloendothelial system escape"and "endosomal esacpe" functions of this nano-micelles for overcoming the biological membrane barrier will also be studied. Mitochondrial targeting evaluation of the puerarin-loaded nano-micelles will be conducted based on the cellular experiments of adjusting the mitochondrial function and animal experiments of reducing the myocardial I/R injury. This research is expected to achieve ischemic myocardial cell mitochondria targeting delivery of drugs, and will lay a basis on the accurat therapy for myocardial ischemia-reperfusion injury.