title: PEGylated peptide based reductive polycations as efficient nonviral gene vectors.
abstract: To overcome the critical barriers in gene delivery, a series of reducible polycations (RPCs) based on low molecular weight (LMW) peptides, i.e. PolyHK6 H, PolyHK6 H-mPEG1 , PolyHK6 H-mPEG2 , and PolyHK6 H-mPEG3 , with different poly(ethylene glycol) (PEG) contents, are synthesized and evaluated as nonviral gene vectors. All the RPCs exhibit lower cytotoxicity compared with 25 kDa polyethyleneimine (PEI) and PEGylated PEI (PEI-mPEG: PEI-mPEG1 , PEI-mPEG2 , and PEI-mPEG3 ). PolyHK6 H-mPEG1 and PolyHK6 H-mPEG2 can bind and condense plasmid deoxyribonucleic acid (pDNA) efficiently with a particle size of about 200 nm. Moreover, they display much higher transfection efficiency than that of 25 kDa PEI especially in serum-supplemented medium. Moreover, PolyHK6 H-mPEG1 has equal transfection efficiency with PEI-mPEG1 which is optimal in the PEI-mPEG, but PolyHK6 H-mPEG1 exhibits significantly lower cytotoxicity than PEI-mPEG1 . This is attributed to the fact that inter-peptide disulfide bonds can increase the stability of RPCs/pDNA complexes in extracellular environment and thereafter cleave in cytoplasm to facilitate the release of pDNA in intracellular environment. The PEGylated RPCs demonstrate here improved intracellular gene transfer performance and will have great potential applications in vivo.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yang
authors.forename: Hui-Yuan
authors.initials: HY
authors.lastname: Wang
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Yi
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Gong
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
authors.forename: Xian-Zheng
authors.initials: XZ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D024202:Electrophoretic Mobility Shift Assay; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry*; D000071228:Polyelectrolytes; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D004247:DNA; D004337:Drug Carriers; D010455:Peptides; D011073:Polyamines; D000071228:Polyelectrolytes; D011092:Polyethylene Glycols