title: Bioreducible guanidinylated polyethylenimine for efficient gene delivery.
abstract: Cationic polymers are known to afford efficient gene transfection. However, cytotoxicity remains a problem at the molecular weight for optimal DNA delivery. As such, optimized polymeric gene delivery systems are still a sought-after research goal. A guanidinylated bioreducible branched polyethylenimine (GBPEI-SS) was synthesized by using a disulfide bond to crosslink the guanidinylated BPEI (GBPEI). GBPEI-SS showed sufficient plasmid DNA (pDNA) condensation ability. The physicochemical properties of GBPEI-SS demonstrate that it has the appropriate size (~200 nm) and surface potential (~30 mV) at a nitrogen-to-phosphorus ratio of 10. No significant toxicity was observed, possibly due to bioreducibility and to the guanidine group delocalizing the positive charge of the primary amine in BPEI. Compared with the nonguanidinylated analogue, BPEI-SS, GBPEI-SS showed enhanced transfection efficiency owing to increased cellular uptake and efficient pDNA release by cleavage of disulfide bonds. This system is very efficient for delivering pDNA into cells, thereby achieving high transfection efficiency and low cytotoxicity.
authors.affiliation: Center for Self-assembly and Complexity, Institute for Basic Science and Department of Chemistry, Pohang University of Science and Technology (POSTECH), San 31, Hyoja-dong, Pohang 790-784 (Republic of Korea).
authors.forename: Duhwan
authors.initials: D
authors.lastname: Lee
authors.forename: Yeong Mi
authors.initials: YM
authors.lastname: Lee
authors.forename: Cherlhyun
authors.initials: C
authors.lastname: Jeong
authors.forename: Jun
authors.initials: J
authors.lastname: Lee
authors.forename: Won Jong
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000378:metabolism; D019791:Guanidine / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D010084:Oxidation-Reduction; D010316:Particle Size; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D014162:Transfection
chemical_list: D057846:Cell-Penetrating Peptides; D011094:Polyethyleneimine; D019791:Guanidine
keywords: cell-penetrating peptides; gene delivery; gene expression; guanidine; polycations; redox chemistry