Treatment of infarcted heart tissue via the capture and local delivery of circulating exosomes through antibody-conjugated magnetic nanoparticles
Treatment of infarcted heart tissue via the capture and local delivery of circulating exosomes through antibody-conjugated magnetic nanoparticles
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DOI：
10.1038/s41551-020-00637-1
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发表时间：
2020-11-01
影响因子：
28.1
通讯作者：
Jin, Yan
中科院分区：
文献类型：
--
作者：
Liu, Shiyu;Chen, Xin;Jin, Yan
内源性细胞外囊泡的全身生物分布是维持组织稳态的核心。在这里，我们表明，梗死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颗粒从循环中收集的外来体的局部积累来改善。该纳米颗粒由Fe3O4核和二氧化硅壳组成，该二氧化硅壳用聚（乙二醇）修饰，通过腙键与两种类型的抗体缀合，所述抗体结合细胞外囊泡表面上的CD63抗原或损伤心肌细胞上的肌球蛋白轻链表面标志物。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腙键的裂解导致捕获的外来体的局部释放。在兔和大鼠心肌梗死模型中，梗死组织中捕获的表达CD63的外来体的磁引导积累导致梗死面积减少以及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，用于治疗其他疾病。磁诱导的循环外泌体从抗体缀合的磁性纳米颗粒聚集和释放到梗死的心脏组织中，改善了大鼠和兔心肌梗死模型中的血管生成和心脏功能。
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.The magnetically induced accumulation and release of circulating exosomes into infarcted heart tissue from antibody-conjugated magnetic nanoparticles improves angiogenesis and heart function in rat and rabbit models of myocardial infarction.