title: CAGW Peptide- and PEG-Modified Gene Carrier for Selective Gene Delivery and Promotion of Angiogenesis in HUVECs in Vivo.
abstract: Gene therapy is a promising strategy for angiogenesis, but developing gene carriers with low cytotoxicity and high gene delivery efficiency in vivo is a key issue. In the present study, we synthesized the CAGW peptide- and poly(ethylene glycol) (PEG)-modified amphiphilic copolymers. CAGW peptide serves as a targeting ligand for endothelial cells (ECs). Different amounts of CAGW peptide were effectively conjugated to the amphiphilic copolymer via heterofunctional poly(ethylene glycol). These CAG- and PEG-modified copolymers could form nanoparticles (NPs) by self-assembly method and were used as gene carriers for the pEGFP-ZNF580 (pZNF580) plasmid. CAGW and PEG modification coordinately improved the hemocompatibility and cytocompatibility of NPs. The results of cellular uptake showed significantly enhanced internalization efficiency of pZNF580 after CAGW modification. Gene expression at mRNA and protein levels demonstrated that EC-targeted NPs possessed high gene delivery efficiency, especially the NPs with higher content of CAGW peptide (1.16 wt %). Furthermore, in vitro and in vivo vascularization assays also showed outstanding vascularization ability of human umbilical vein endothelial cells treated by the NP/pZNF580 complexes. This study demonstrates that the CAGW peptide-modified NP is a promising candidate for gene therapy in angiogenesis.
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University , Yaguan Road 135, Tianjin 300350, China.|Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin) , Weijin Road 92, Tianjin 300072, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University , Yaguan Road 135, Tianjin 300350, China.|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: School of Chemical Engineering and Technology, Tianjin University , Yaguan Road 135, Tianjin 300350, China.|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: School of Chemical Engineering and Technology, Tianjin University , Yaguan Road 135, Tianjin 300350, China.
authors.forename: Mary
authors.initials: M
authors.lastname: Akpanyung
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University , Yaguan Road 135, Tianjin 300350, China.
authors.forename: Abdelilah
authors.initials: A
authors.lastname: Nejjari
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University , Yaguan Road 135, Tianjin 300350, China.
authors.forename: Agnaldo Luis
authors.initials: AL
authors.lastname: Neve
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University , Yaguan Road 135, Tianjin 300350, China.|Tianjin University-Helmholtz-Zentrum Geesthacht , Joint Laboratory for Biomaterials and Regenerative Medicine, Yaguan Road 135, Tianjin 300350, China.
authors.forename: Xiangkui
authors.identifier: http://orcid.org/0000-0001-7894-9361
authors.initials: X
authors.lastname: Ren
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University , Yaguan Road 135, Tianjin 300350, China.|Tianjin University-Helmholtz-Zentrum Geesthacht , Joint Laboratory for Biomaterials and Regenerative Medicine, Yaguan Road 135, Tianjin 300350, China.
authors.forename: Jintang
authors.initials: J
authors.lastname: Guo
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University , Yaguan Road 135, Tianjin 300350, China.|Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin) , Weijin Road 92, Tianjin 300072, China.|Tianjin University-Helmholtz-Zentrum Geesthacht , Joint Laboratory for Biomaterials and Regenerative Medicine, Yaguan Road 135, Tianjin 300350, China.|Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University , Weijin Road 92, Tianjin 300072, China.
authors.forename: Yakai
authors.identifier: http://orcid.org/0000-0002-4511-0874
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Institute of Biomaterials and Engineering, Wenzhou Medical University , Wenzhou, Zhejiang 325011, China.|Wenzhou Institute of Biomaterials and Engineering, CNITECH, CAS , Wenzhou, Zhejiang 325011, China.
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 300162, China.
authors.forename: Wencheng
authors.initials: W
authors.lastname: Zhang
mesh_terms: D002478:Cells, Cultured; D004337:Drug Carriers; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D053758:Nanoparticles; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols; D014157:Transcription Factors
chemical_list: D004337:Drug Carriers; D010455:Peptides; D014157:Transcription Factors; C550122:ZNF580 protein, human; D011092:Polyethylene Glycols
keywords: CAG; HUVECs; PEG; angiogenesis; gene carriers; pZNF580; peptide