Treatment of infarcted heart tissue via the capture and local delivery of circulating exosomes through antibody-conjugated magnetic nanoparticles.
Shiyu LiuXin ChenLili BaoTao LiuPingyun YuanXiaoshan YangXinyu QiuJohn Justin GoodingYongkang BaiJiajia XiaoFengxing PuYan JinPublished in: Nature biomedical engineering (2020)
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.
Keyphrases
- magnetic nanoparticles
- mesenchymal stem cells
- ejection fraction
- heart failure
- stem cells
- endothelial cells
- left ventricular
- atrial fibrillation
- aortic stenosis
- oxidative stress
- dendritic cells
- acute myocardial infarction
- vascular endothelial growth factor
- pet imaging
- pulmonary artery
- computed tomography
- mitral valve
- coronary artery
- bone marrow
- immune response
- pet ct
- positron emission tomography
- high glucose