title: Polyethylenimine-grafted copolymer of poly(l-lysine) and poly(ethylene glycol) for gene delivery.
abstract: A major challenge in gene therapy is the development of effective gene delivery vectors with low toxicity. In the present study, linear poly(ethylenimine) (lPEI) with low molecular weight was grafted onto the block copolymer (PPL) of poly(l-lysine) (PLL) and poly(ethylene glycol)(PEG), yielding a ternary copolymer PEG-b-PLL-g-lPEI (PPI) for gene delivery. In such molecular design, PLL, lPEI and PEG blocks were expected to render the vector biodegradability, proton buffering capacity, low cationic toxicity and potentially long circulation in vivo, respectively. Given proper control of molecular composition, the copolymers demonstrated lower cytotoxicity, proton buffering capacity, ability to condense pDNA and mediate effective gene transfection in various cell lines. With folate as an exemplary targeting ligand, the FA-PPI/pDNA complex showed much higher transgene activity than its nontargeting counterpart for both reporter and therapeutic genes in folate receptor(FR)-positive cells. FA-PPI mediated effective transfection of the TNF-related apoptosis-inducing ligand gene (TRAIL) in human hepatoma Bel 7402 cells, leading to cell apoptosis and great suppression of cell viability. Our results indicate that the copolymers might be a promising vector combining low cytotoxicity, biodegradability, and high gene transfection efficiency.
authors.affiliation: PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Dai
authors.forename: Seyin
authors.initials: S
authors.lastname: Zou
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Pei
authors.forename: Du
authors.initials: D
authors.lastname: Cheng
authors.forename: Hua
authors.initials: H
authors.lastname: Ai
authors.forename: Xintao
authors.initials: X
authors.lastname: Shuai
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000009:adverse effects / Q000737:chemistry*; D006801:Humans; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry; D011108:Polymers / Q000009:adverse effects / Q000737:chemistry*
chemical_list: D011108:Polymers; D011107:Polylysine; D011092:Polyethylene Glycols; D011094:Polyethyleneimine