Delivery of microRNA-1 inhibitor by dendrimer-based nanovector: An early targeting therapy for myocardial infarction in mice.
Delivery of microRNA-1 inhibitor by dendrimer-based nanovector: An early targeting therapy for myocardial infarction in mice.
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DOI：
10.1016/j.nano.2017.12.004
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发表时间：
2017-12
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影响因子：
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通讯作者：
Xiaomei Xue;Xueyin Shi;Haiqing Dong;Shasha You;H. Cao;Kun Wang;Ya Wen;Donglu Shi;Bin He;Yongyong Li
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文献类型：
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作者：
Xiaomei Xue;Xueyin Shi;Haiqing Dong;Shasha You;H. Cao;Kun Wang;Ya Wen;Donglu Shi;Bin He;Yongyong Li
心肌梗死（MI），已知是快速进展和致命的，需要及时和有效的干预，特别是在黄金24小时内。关键是开发一种能够早期靶向梗死部位并具有综合治疗能力的治疗剂。发现心肌梗死后24 h AT1受体表达最高，我们开发了一种锚定有AT1靶向肽的纳米载体（AT1-PEG-DGL），同时用特异性microRNA-1抑制剂（AMO-1）武装它以减轻心肌细胞凋亡。IV给药后的体内成像表明，AT1-PEG-DGL在所需的早期在MI心脏中迅速蓄积，显著优于未靶向AT1的对照组。最重要的是，在单次IV注射后观察到显著的体内抗凋亡作用。心肌梗死边缘区细胞凋亡明显减少，心肌梗死面积较对照组缩小64.1%，为早期治疗心肌梗死提供了可能。
Myocardial infarction (MI), known to be rapidly progressed and fatal, necessitates a timely and effective intervention particularly within golden 24 h. The crux is to develop a therapeutic agent that can early target the infarct site with integrated therapeutic capacity. Finding the AT1receptor being most over-expressed at 24 h after MI, we developed a nanovector (AT1-PEG-DGL) anchored with AT1targeting peptide, and simultaneously armed it with specific microRNA-1 inhibitor (AMO-1) to attenuate cardiomyocyte apoptosis. In vivo imaging after IV administration demonstrated that AT1-PEG-DGL quickly accumulated in the MI heart during the desired early period, significantly outperforming the control group without AT1targeting. Most importantly, a pronounced in-vivo anti-apoptosis effect was observed upon a single IV injection. Apoptotic cell death in the infarct border zone was significantly decreased and the myocardial infarct size was reduced by 64.1% as compared with that in MI control group, promising for early MI treatment.