title: CREDVW-Linked Polymeric Micelles As a Targeting Gene Transfer Vector for Selective Transfection and Proliferation of Endothelial Cells.
abstract: Nowadays, gene transfer technology has been widely used to promote endothelialization of artificial vascular grafts. However, the lack of gene vectors with low cytotoxicity and targeting function still remains a pressing challenge. Herein, polyethylenimine (PEI, 1.8 kDa or 10 kDa) was conjugated to an amphiphilic and biodegradable diblock copolymer poly(ethylene glycol)-b-poly(lactide-co-glycolide) (mPEG-b-PLGA) to prepare mPEG-b-PLGA-g-PEI copolymers with the aim to develop gene vectors with low cytotoxicity while high transfection efficiency. The micelles were prepared from mPEG-b-PLGA-g-PEI copolymers by self-assembly method. Furthermore, Cys-Arg-Glu-Asp-Val-Trp (CREDVW) peptide was linked to micelle surface to enable the micelles with special recognition for endothelial cells (ECs). In addition, pEGFP-ZNF580 plasmids were condensed into these CREDVW-linked micelles to enhance the proliferation of ECs. These CREDVW-linked micelle/pEGFP-ZNF580 complexes exhibited low cytotoxicity by MTT assay. The cell transfection results demonstrated that pEGFP-ZNF580 could be transferred into ECs efficiently by these micelles. The results of Western blot analysis showed that the relative ZNF580 protein level in transfected ECs increased to 76.9%. The rapid migration of transfected ECs can be verified by wound healing assay. These results indicated that CREDVW-linked micelles could be a suitable gene transfer vector with low cytotoxicity and high transfection efficiency, which has great potential for rapid endothelialization of artificial blood vessels.
authors.affiliation: §Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Weijin Road 92, Tianjin 300072, China.
authors.forename: Xuefang
authors.initials: X
authors.lastname: Hao
authors.affiliation: §Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Weijin Road 92, Tianjin 300072, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: §Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Weijin Road 92, Tianjin 300072, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Lv
authors.affiliation: §Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Weijin Road 92, Tianjin 300072, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.forename: Xiangkui
authors.initials: X
authors.lastname: Ren
authors.affiliation: ⊥Joint Laboratory for Biomaterials and Regenerative Medicine, Tianjin University-Helmholtz-Zentrum Geesthacht, Weijin Road 92, Tianjin 300072, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: §Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Weijin Road 92, Tianjin 300072, China.|⊥Joint Laboratory for Biomaterials and Regenerative Medicine, Tianjin University-Helmholtz-Zentrum Geesthacht, Weijin Road 92, Tianjin 300072, China.
authors.forename: Yakai
authors.initials: Y
authors.lastname: Feng
authors.affiliation: #Department of Physiology and Pathophysiology, Logistics University of Chinese People's Armed Police Force, Tianjin 300162, China.
authors.forename: Wencheng
authors.initials: W
authors.lastname: Zhang
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects*; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000187:drug effects*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008823:Micelles; D011091:Polyesters; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000737:chemistry; D011098:Polyglactin 910 / Q000008:administration & dosage / Q000737:chemistry; D014162:Transfection; D058017:Vascular Grafting / Q000379:methods; D014945:Wound Healing
chemical_list: D008823:Micelles; D011091:Polyesters; C558447:methoxypolyethyleneglycol-poly(lactic-co-glycolic acid); D011098:Polyglactin 910; D011092:Polyethylene Glycols; D011094:Polyethyleneimine
keywords: endothelial cells; gene vector; micelles; peptide; polyethylenimine; targeting