School of Materials Science and Engineering, and Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300350, China.
School of Materials Science and Engineering, and Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300350, China.
Colloids Surf B Biointerfaces. 2019 Oct 1;182:110369. doi: 10.1016/j.colsurfb.2019.110369. Epub 2019 Jul 15.
Restenosis is still one of the main challenges in small-diameter vascular regeneration, and effective modulation of vascular smooth muscle cells (SMCs) is essential to cope with the related issues. As one of microRNAs (miRNAs) in vascular systems, miRNA-145 can regulate SMCs in the normal contractile phenotype, and inhibit the excessive proliferation and intimal hyperplasia. Herein, VAPG peptide-modified trimethyl chitosan-g-poly(ethylene glycol) (TMC-g-PEG-VAPG) was developed specially for target-delivery of miRNA-145 to SMCs to fulfill the proper function. The TMC-g-PEG-VAPG/miRNA-145 complexes exhibited low cytotoxicity, and TMC-g-PEG-VAPG with relatively higher molecular weight of chitosan (50 kDa) could significantly enhance cellular uptake in SMCs. Moreover, loading with TMC-g-PEG-VAPG/miRNA-145 complexes, the electrospun membranes of poly(ethylene glycol)-b-poly(L-lactide-co-ε-caprolactone) were capable of controlling SMCs at gene and protein levels on day 3 by targeting Krüppel-like factor 4 to increase the expression of myocardin and α-smooth muscle actin. Furthermore, miRNA-145 released from the electrospun membranes also showed in vitro bioactivity of modulating the contractile phenotype of SMCs in the prolonged duration, at least 56 days. The functional electrospun membranes containing TMC-g-PEG-VAPG/miRNA-145 complexes may have a great potential in the application of small-diameter blood vessel regeneration.
血管再狭窄仍然是小直径血管再生的主要挑战之一，有效调节血管平滑肌细胞（SMC）对于应对相关问题至关重要。miRNA-145 是血管系统中的一种 microRNA，可调节正常收缩表型的 SMC，并抑制过度增殖和内膜增生。本文中，专门开发了 VAPG 肽修饰的三甲基壳聚糖-g-聚乙二醇（TMC-g-PEG-VAPG）用于将 miRNA-145 靶向递送至 SMC，以发挥适当的功能。TMC-g-PEG-VAPG/miRNA-145 复合物表现出低细胞毒性，并且相对较高分子量的壳聚糖（50 kDa）的 TMC-g-PEG-VAPG 可显著增强 SMC 中的细胞摄取。此外，负载有 TMC-g-PEG-VAPG/miRNA-145 复合物的聚乙二醇-b-聚（L-丙交酯-co-ε-己内酯）电纺膜能够通过靶向 Krüppel 样因子 4 来控制 SMC 在第 3 天的基因和蛋白水平，从而增加心肌抑制因子和 α-平滑肌肌动蛋白的表达。此外，从电纺膜释放的 miRNA-145 在体外也表现出调节 SMC 收缩表型的生物活性，持续时间至少为 56 天。含有 TMC-g-PEG-VAPG/miRNA-145 复合物的功能电纺膜在小直径血管再生的应用中具有很大的潜力。
