Treatment of infarcted heart tissue via the capture and local delivery of circulating exosomes through antibody-conjugated magnetic nanoparticles

被引：228

作者：

Liu, Shiyu ^{[1
,2
,3
,4
]}

Chen, Xin ^{[5
]}

Bao, Lili ^{[1
,2
,3
,4
]}

Liu, Tao ^{[5
]}

Yuan, Pingyun ^{[5
]}

Yang, Xiaoshan ^{[1
,2
,3
,4
]}

Qiu, Xinyu ^{[1
,2
,3
,4
]}

Gooding, J. Justin ^{[6
,7
]}

Bai, Yongkang ^{[5
]}

Xiao, Jiajia ^{[4
]}

Pu, Fengxing ^{[4
]}

Jin, Yan ^{[1
,2
,3
,4
]}

机构：

[1] Fourth Mil Med Univ, Ctr Tissue Engn, State Key Lab Mil Stomatol, Xian, Peoples R China

[2] Fourth Mil Med Univ, Ctr Tissue Engn, Natl Clin Res Ctr Oral Dis, Xian, Peoples R China

[3] Fourth Mil Med Univ, Ctr Tissue Engn, Shaanxi Key Lab Oral Dis, Xian, Peoples R China

[4] Fourth Mil Med Univ, Cardiovasc Res Ctr, Ctr Tissue Engn, Xian, Shaanxi, Peoples R China

[5] Xi An Jiao Tong Univ, Inst Polymer Sci Chem Engn, Shaanxi Key Lab Energy Chem Proc Intensificat, Sch Chem Engn & Technol, Xian, Peoples R China

[6] Univ New South Wales, Australian Ctr NanoMed, Sch Chem, Sydney, NSW, Australia

[7] Univ New South Wales, ARC Australian Ctr Excellence Convergent Bionano, Sydney, NSW, Australia

来源：

NATURE BIOMEDICAL ENGINEERING | 2020年 / 4卷 / 11期

基金：

澳大利亚研究理事会; 中国国家自然科学基金;

关键词：

CARDIOSPHERE-DERIVED CELLS; MYOCARDIAL-INFARCTION; EXTRACELLULAR VESICLES; STEM-CELLS; CANCER; REPAIR; ANGIOGENESIS; PERFORMANCE; BIOGENESIS; PROTECT;

D O I：

10.1038/s41551-020-00637-1

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

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.

引用

页码：1063 / +

页数：16

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