The systemic biodistribution of endogenous extracellular vesicles is central to the maintenance of tissue homeostasis. Here, we show that angiogenesis and heart function in infarcted heart tissue can be ameliorated by the local accumulation of exosomes collected from circulation using magnetic nanoparticles. The nanoparticles consist of a Fe₃O₄ core and a silica shell that is decorated with poly (ethylene glycol) conjugated through hydrazone bonds to two types of antibody, which bind either to CD63 antigens on the surface of extracellular vesicles or to myosin-light-chain surface markers on injured cardiomyocytes. On application of a local magnetic field, accumulation of the nanoparticles and cleavage of the hydrazone bonds under the acidic pH of injured cardiac tissue lead to the local release of the captured exosomes. In rabbit and rat models of myocardial infarction, the magnetic-guided accumulation of captured CD63-expressing exosomes in infarcted tissue led to reductions in infarct size as well as improved left-ventricle ejection fraction and angiogenesis. The approach could be used to manipulate endogenous exosome biodistribution for the treatment of other diseases.

内源性细胞外囊泡的全身生物分布对于维持组织动态平衡至关重要。在这里，我们显示梗死性心脏组织中的血管生成和心脏功能可以通过使用磁性纳米粒子从循环中收集的外来体的局部积累而得到改善。纳米颗粒由Fe ₃ O _4组成核心和硅胶壳，装饰有通过键与两种类型的抗体偶联的聚（乙二醇），两种抗体与细胞外小泡表面的CD63抗原或受损的心肌细胞上的肌球蛋白轻链表面标记结合。在施加局部磁场时，在受损心脏组织的酸性pH下纳米颗粒的积累和the键的断裂导致捕获的囊泡的局部释放。在心肌梗塞的兔子和大鼠模型中，在梗死组织中磁性捕获的表达CD63的外泌体的磁性引导积累导致梗死面积的减小以及左心室射血分数和血管生成的改善。该方法可用于操纵内源性外泌体生物分布，以治疗其他疾病。