Lv Juan, Hao Xuefang, Li Qian, Akpanyung Mary, Nejjari Abdelilah, Neve Agnaldo Luis, Ren Xiangkui, Feng Yakai, Shi Changcan, Zhang Wencheng
School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Tianjin 300350, China.
Institute of Biomaterials and Engineering, Wenzhou Medical University, Wenzhou, Zhejiang 325011, China and Wenzhou Institute of Biomaterials and Engineering, CNITECH, CAS, Wenzhou, Zhejiang 325011, China.
Biomater Sci. 2017 Feb 28;5(3):511-522. doi: 10.1039/c6bm00856a.
In this work, a biodegradable star-shaped copolymer poly(lactide-co-3(S)-methyl-morpholine-2,5-dione) (Star-(PLMD)) was synthesized via ring-opening polymerization (ROP), and subsequently a gene carrier Star-PLMD-g-PEI-g-PEG-CREDVW was prepared by grafting polyethyleneimine (PEI), polyethylene glycol (PEG) and targeting peptide REDV onto Star-(PLMD). This gene carrier could form stable micelles to condense pEGFP-ZNF580 through electrostatic interaction. The resulting complexes were biocompatible and showed high efficiency in gene delivery. In addition, these complexes exhibited high selectivity for endothelial cells (ECs), high transfection efficiency and enhanced migration of ECs. The protein level of ZNF580 expression was significantly high (up to 85%), while the control group was only 51%. This combination of degradability, targeting ligand and star-structure strategy exhibits a significant advantage in transfection efficiency and migration of ECs.
在本研究中,通过开环聚合(ROP)合成了一种可生物降解的星形共聚物聚(丙交酯 - 共 - 3(S)-甲基 - 吗啉 - 2,5 - 二酮)(Star-(PLMD)),随后通过将聚乙烯亚胺(PEI)、聚乙二醇(PEG)和靶向肽REDV接枝到Star-(PLMD)上制备了基因载体Star-PLMD-g-PEI-g-PEG-CREDVW。该基因载体可通过静电相互作用形成稳定的胶束以凝聚pEGFP-ZNF580。所得复合物具有生物相容性,并在基因递送中显示出高效率。此外,这些复合物对内皮细胞(ECs)表现出高选择性、高转染效率并增强了ECs的迁移。ZNF580表达的蛋白质水平显著较高(高达85%),而对照组仅为51%。这种可降解性、靶向配体和星形结构策略的组合在ECs的转染效率和迁移方面表现出显著优势。