title: Tyroserleutide-based gene vector for suppressing VEGF expression in cancer therapy.
abstract: A small interfering RNA (siRNA) plasmid DNA (pYr-1.1-hU6-EGFP-siVEGF) was constructed and used for suppressing vascular endothelial growth factor (VEGF) expression and inhibiting tumor growth. Then, a (tyrosyl-seryl-leucine)-polyethyleneimine-poly(ethylene glycol) (YSL-PEI-PEG) conjugate was designed and synthesized as a gene carrier for the delivery of pYr-1.1-hU6-EGFP-siVEGF plasmid. The therapeutic peptide YSL was conjugated to PEI to improve the anti-cancer efficiency, and the PEG chain was introduced to reduce the serum protein adsorption and improve the stability of the complex in the systemic circulation. It was found that YSL-PEI-PEG could efficiently condense plasmid DNA when the vector/DNA weight ratio was higher than 2. Compared with PEI 25 kDa, YSL-PEI-PEG exhibited higher transfection efficiency and lower cytotoxicity. More importantly, the results showed that the gene delivery system owned strong ability to inhibit cancer cell proliferation in vitro and tumor growth in vivo. YSL-PEI-PEG has great potential as a gene vector for clinical applications.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
authors.forename: Hui-Yuan
authors.initials: HY
authors.lastname: Wang
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Yi
authors.forename: Si-Yong
authors.initials: SY
authors.lastname: Qin
authors.forename: Cao
authors.initials: C
authors.lastname: Li
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
authors.forename: Xian-Zheng
authors.initials: XZ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009842:Oligopeptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D011094:Polyethyleneimine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D011108:Polymers; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D009842:Oligopeptides; D011108:Polymers; D042461:Vascular Endothelial Growth Factor A; C544016:poly(ethylene glycol)-co-poly(ethyleneimine); D011092:Polyethylene Glycols; D011094:Polyethyleneimine; C484773:H-Tyr-Ser-Leu-OH