State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Center for Tissue Engineering, Fourth Military Medical University, Xi'an, China.
Cardiovascular Research Center, Center for Tissue Engineering, Fourth Military Medical University, Xi'an, China.
Nat Biomed Eng. 2020 Nov;4(11):1063-1075. doi: 10.1038/s41551-020-00637-1. Epub 2020 Nov 6.
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 FeO 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分布对于维持组织内稳态至关重要。在这里，我们表明，通过使用磁性纳米粒子从循环中收集的外泌体的局部积累，可以改善梗塞组织中的血管生成和心脏功能。这些纳米粒子由 FeO 核和硅壳组成，硅壳通过腙键修饰有聚乙二醇，通过腙键连接到两种类型的抗体，一种抗体与细胞外囊泡表面的 CD63 抗原结合，另一种抗体与损伤的心肌细胞表面的肌球蛋白轻链标志物结合。在施加局部磁场的情况下，纳米粒子的积累和解离酸性 pH 值下损伤心脏组织中的腙键导致捕获的外泌体的局部释放。在兔和大鼠心肌梗死模型中，磁性引导的捕获 CD63 表达的外泌体在梗塞组织中的积累导致梗塞面积减少，左心室射血分数和血管生成改善。该方法可用于操纵内源性外泌体的生物分布，以治疗其他疾病。
