title: Regulation of the endothelialization by human vascular endothelial cells by ZNF580 gene complexed with biodegradable microparticles.
abstract: The lack of living endothelial cells (ECs) functional layer is one of the major reasons which account for thrombosis of synthetic vascular vessels. To overcome this obstacle, we employed ZNF580 gene complexed with biodegradable microparticles (MPs) to promote the rapid endothelialization by ECs. In order to realize the controlled release of ZNF580 gene from MPs/gene complexes, a series of amphiphilic triblock copolymers with different degradation rate, namely, methoxy-poly(ethylene glycol)-block-poly(3(S)-methyl-morpholine-2,5-dione)-graft-polyethyleneimine (mPEG-b-PMMD-g-PEI), methoxy-poly(ethylene glycol)-block-poly(3(S)-methyl-morpholine-2,5-dione-co-lactide)-graft-polyethyleneimine (mPEG-b-P(MMD-co-LA)-g-PEI) and methoxy-poly(ethylene glycol)-block-poly(3(S)-methyl-morpholine-2,5-dione-co-lactide-co-glycolide)-graft-polyethyleneimine (mPEG-b-P(MMD-co-LA-co-GA)-g-PEI), were synthesized. Then, MPs were formed by self-assembly. The hydrophobic cores of these MPs were composed of PMMD, P(MMD-LA) or P(MMD-co-LA-co-GA) segments, and provided crosslinking points for numbers of PEG and short PEI chains to form a high hydrophilic and positive charged corona/shell structure. Based on their positive charged surface, MPs can compact pEGFP-ZNF580 into MPs/pEGFP-ZNF580 complexes. The cell transfection result demonstrated that pEGFP-ZNF580 could be transported efficiently into ECs by these complexes. The result of western blot showed that the relative ZNF580 protein level can increase to 35.74%-46.11% by the overexpression of ZNF580 gene. Furthermore, the release of pEGFP-ZNF580 could be sustained at least 25 days due to the controllable degradation ability of the hydrophobic MPs' core. The MPs and MPs/pEGFP-ZNF580 complexes showed low cytotoxicity because of the introduction of PEG chains and low molecular weight PEI on the surface of these MPs. Notably, at the low concentration (20 μg/mL), the MPs and their complexes were non-cytotoxicity. The rapid endothelialization was promoted significantly by the expression of pEGFP-ZNF580.
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Changcan
authors.initials: C
authors.lastname: Shi
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China; Key Laboratory of Systems Bioengineering of Ministry of Education, Tianjin University, Tianjin 300072, China; Tianjin University-Helmholtz-Zentrum Geesthacht, Joint Laboratory for Biomaterials and Regenerative Medicine, Tianjin 300072, China.
authors.forename: Fanglian
authors.initials: F
authors.lastname: Yao
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Musammir
authors.initials: M
authors.lastname: Khan
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Xiangkui
authors.initials: X
authors.lastname: Ren
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China; Key Laboratory of Systems Bioengineering of Ministry of Education, Tianjin University, Tianjin 300072, China; Tianjin University-Helmholtz-Zentrum Geesthacht, Joint Laboratory for Biomaterials and Regenerative Medicine, Tianjin 300072, China; Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Tianjin 300072, China. Electronic address: yakaifeng@tju.edu.cn.
authors.forename: Yakai
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Graduate School of Tianjin Medical University, Tianjin 300070, China.
authors.forename: Jiawen
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Physiology and Pathophysiology, Logistics University of Chinese People's Armed Police Force, Tianjin 300162, China. Electronic address: wenchengzhang@yahoo.com.
authors.forename: Wencheng
authors.initials: W
authors.lastname: Zhang
mesh_terms: D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D011108:Polymers; D014157:Transcription Factors; C550122:ZNF580 protein, human
keywords: Biodegradable; Microparticles; Non-viral gene carrier; Rapid endothelialization; Triblock copolymers; ZNF580 gene