Nanofiber-mediated microRNA-126 delivery to vascular endothelial cells for blood vessel regeneration
Nanofiber-mediated microRNA-126 delivery to vascular endothelial cells for blood vessel regeneration
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纳米纤维介导的 microRNA-126 递送至血管内皮细胞以促进血管再生
DOI：
10.1016/j.actbio.2016.07.048
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发表时间：
2016
影响因子：
9.7
通讯作者：
Yuan Xiaoyan
中科院分区：
文献类型：
--
作者：
Zhou Fang;Jia Xiaoling;Yang Yang;Yang Qingmao;Gao Chao;Hu Suli;Zhao Yunhui;Fan Yubo;Yuan Xiaoyan
由于通过microRNA（miRNAs）操纵基因表达是心血管疾病治疗的新兴策略之一，因此将miRNAs局部递送至特定血管组织是具有挑战性的。在这项工作中，我们开发了一种由静电纺丝纤维膜和靶向载体组成的有效递送系统，用于在局部特定的血管环境中将miRNA-126（miR-126）细胞内递送到血管内皮细胞（VECs）。采用乳液静电纺丝法制备了聚乙二醇-b-聚（L-丙交酯-co-ε-己内酯）共聚物（PELCL），并采用双电源静电纺丝法制备了聚ε-己内酯（PCL）和明胶双层血管支架。PELCL的内层负载有miR-126在REDV肽修饰的三甲基壳聚糖-g-聚乙二醇中的复合物，调节了VEC的反应，而PCL/明胶的外层有助于机械稳定性。通过细胞增殖和miR-126靶基因的SPRED-1表达来评价负载miR-126的电纺膜的生物活性。通过将miR-126的靶向复合物包封在电纺膜中，获得了持续56天的miRNA的持续释放曲线。在第3天检测到VEC中SPRED-1基因表达的显著下调，并且发现从电纺膜释放的miR-126在前9天加速VEC增殖。负载miR-126复合物的双层血管支架在体内也可以改善内皮化。这些结果证明了这种方法的潜力，朝着一个新的和更有效的交付系统的局部交付的miRNA，以促进血管regeneration.Statement的显著性组织工程的小直径血管仍然是具有挑战性的，因为血栓形成和低的长期通畅性。通过miRNAs调控基因表达可能成为血管再生的一种新策略。在这里，我们报告了一种有效的电纺纤维支架与REDV肽修饰的三甲基壳聚糖结合的递送系统，用于在局部血管环境中将miR-126靶向细胞内递送至VEC。结果表明，miR-126可通过下调SPRED-1基因表达而调控VEC增殖。电纺支架负载靶向递送载体可作为血管组织工程中局部递送miRNAs的理想平台。
As manipulation of gene expression by virtue of microRNAs (miRNAs) is one of the emerging strategies for cardiovascular disease remedy, local delivery of miRNAs to a specific vascular tissue is challenging. In this work, we developed an efficient delivery system composed of electrospun fibrous membranes and target carriers for the intracellular delivery of miRNA-126 (miR-126) to vascular endothelial cells (VECs) in the local specific vascular environment. A bilayer vascular scaffold was specially prepared via emulsion electrospinning of poly(ethylene glycol)-b-poly(l-lactide-co-ε-caprolactone) (PELCL) and dual-power electrospinning of poly(ε-caprolactone) (PCL) and gelatin. The inner layer of PELCL, which was loaded with complexes of miR-126 in REDV peptide-modified trimethyl chitosan-g-poly(ethylene glycol), regulated the response of VECs, while the outer layer of PCL/gelatin contributed to the mechanical stability. Biological activities of the miR-126-loaded electrospun membranes were evaluated by cell proliferation and SPRED-1 expression of a miR-126 target gene. By encapsulating targeting complexes of miR-126 in the electrospun membranes, a sustained release profile of miRNA was obtained for 56 days. Significant down-regulation of SPRED-1 gene expression in VECs was detected on day 3, and it was found that miR-126 released from the electrospun membranes accelerated VEC proliferation in the first 9 days. The bilayer vascular scaffold loaded with miR-126 complexes could also improve endothelializationin vivo. These results demonstrated the potential of this approach towards a new and more effective delivering system for local delivery of miRNAs to facilitate blood vessel regeneration.Statement of SignificanceTissue engineering of small-diameter blood vessels is still challenging because of thrombosis and low long-term patency. The manipulation of gene expression by miRNAs could be a novel strategy in vascular regeneration. Here, we report an efficient delivery system of electrospun fibrous scaffold combined with REDV peptide-modified trimethyl chitosan for targeted intracellular delivery of miR-126 to VECs in the local vascular environment. Results exhibited that miR-126 released from the electrospun membrane could modulate VEC proliferation via down-regulation of SPRED-1 gene expression. The electrospun scaffolds loaded with target-delivery carriers may serve as an ideal platform for local delivery of miRNAs in the vascular tissue engineering.