title: Co-self-assembly of cationic microparticles to deliver pEGFP-ZNF580 for promoting the transfection and migration of endothelial cells.
abstract: The gene transfection efficiency of polyethylenimine (PEI) varies with its molecular weight. Usually, high molecular weight of PEI means high gene transfection, as well as high cytotoxicity in gene delivery in vivo. In order to enhance the transfection efficiency and reduce the cytotoxicity of PEI-based gene carriers, a novel cationic gene carrier was developed by co-self-assembly of cationic copolymers. First, a star-shaped copolymer poly(3(S)-methyl-morpholine-2,5-dione-co-lactide) (P(MMD-co-LA)) was synthesized using D-sorbitol as an initiator, and the cationic copolymer (P(MMD-co-LA)-g-PEI) was obtained after grafting low-molecular weight PEI. Then, by co-self-assembly of this cationic copolymer and a diblock copolymer methoxy-poly(ethylene glycol) (mPEG)-b-P(MMD-co-LA), microparticles (MPs) were formed. The core of MPs consisted of a biodegradable block of P(MMD-co-LA), and the shell was formed by mPEG and PEI blocks. Finally, after condensation of pEGFP-ZNF580 by these MPs, the plasmids were protected from enzymatic hydrolysis effectively. The result indicated that pEGFP-ZNF580-loaded MP complexes were suitable for cellular uptake and gene transfection. When the mass ratio of mPEG-b-P(MMD-co-LA) to P(MMD-co-LA)-g-PEI reached 3/1, the cytotoxicity of the complexes was very low at low concentration (20 μg mL-1). Additionally, pEGFP-ZNF580 could be transported into endothelial cells (ECs) effectively via the complexes of MPs/pEGFP-ZNF580. Wound-healing assay showed that the transfected ECs recovered in 24 h. Cationic MPs designed in the present study could be used as an applicable gene carrier for the endothelialization of artificial blood vessels.
authors.affiliation: Department of Polymer Science and Engineering, School of Chemical Engineering and Technology, Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Tianjin University; Tianjin University-Helmholtz-Zentrum Geesthacht, Joint Laboratory for Biomaterials and Regenerative Medicine; Key Laboratory of Systems Bioengineering of Ministry of Education, Tianjin University, Tianjin; Institute of Biomaterials and Engineering, Wenzhou Medical University; Wenzhou Institute of Biomaterials and Engineering, CNITECH, CAS, Wenzhou.
authors.forename: Yakai
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Polymer Science and Engineering, School of Chemical Engineering and Technology, Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Tianjin University.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Polymer Science and Engineering, School of Chemical Engineering and Technology, Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Tianjin University.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Polymer Science and Engineering, School of Chemical Engineering and Technology, Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Tianjin University.
authors.forename: Xuefang
authors.initials: X
authors.lastname: Hao
authors.affiliation: Department of Polymer Science and Engineering, School of Chemical Engineering and Technology, Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Tianjin University.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Polymer Science and Engineering, School of Chemical Engineering and Technology, Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Tianjin University; Tianjin University-Helmholtz-Zentrum Geesthacht, Joint Laboratory for Biomaterials and Regenerative Medicine.
authors.forename: Xiangkui
authors.initials: X
authors.lastname: Ren
authors.affiliation: Institute of Biomaterials and Engineering, Wenzhou Medical University; Wenzhou Institute of Biomaterials and Engineering, CNITECH, CAS, Wenzhou.
authors.forename: Changcan
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Physiology and Pathophysiology, Logistics University of Chinese People's Armed Police Force, Tianjin, People's Republic of China.
authors.forename: Wencheng
authors.initials: W
authors.lastname: Zhang
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D001807:Blood Vessel Prosthesis; D002412:Cations; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D004247:DNA / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006801:Humans; D008970:Molecular Weight; D009025:Morpholines / Q000737:chemistry*; D010316:Particle Size; D010957:Plasmids; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D012685:Sepharose / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D014157:Transcription Factors / Q000737:chemistry*; D014162:Transfection
chemical_list: D001672:Biocompatible Materials; D002412:Cations; D009025:Morpholines; D011108:Polymers; D014157:Transcription Factors; C550122:ZNF580 protein, human; C520636:morpholine-2,5-dione; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; C028210:monomethoxypolyethylene glycol; D004247:DNA; D012685:Sepharose
keywords: endothelial cells; gene carrier; microparticles; migration; star-shaped copolymer; transfection