title: Shedding PEG Palisade by Temporal Photostimulation and Intracellular Reducing Milieu for Facilitated Intracellular Trafficking and DNA Release.
abstract: The dilemma of poly(ethylene glycol) surface modification (PEGylation) inspired us to develop an intracellularly sheddable PEG palisade for synthetic delivery systems. Here, we attempted to conjugate PEG to polyethylenimine (PEI) through tandem linkages of disulfide-bridge susceptible to cytoplasmic reduction and an azobenzene/cyclodextrin inclusion complex responsive to external photoirradiation. The subsequent investigations revealed that facile PEG detachment could be achieved in endosomes upon photoirradiation, consequently engendering exposure of membrane-disruptive PEI for facilitated endosome escape. The liberated formulation in the cytosol was further subjected to complete PEG detachment relying on disulfide cleavage in the reductive cytosol, thus accelerating dissociation of electrostatically assembled PEI/DNA polyplex to release DNA by means of polyion exchange reaction with intracellularly charged species, ultimately contributing to efficient gene expression.
authors.affiliation: School of Chemistry and Chemical Engineering, Tianjin Key Laboratory of Organic Solar Cells and Photochemical Conversion, Tianjin University of Technology , 391 Binshui Xidao, Tianjin, Xiqing District, 300384, China.
authors.forename: Tieyan
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Qixian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: School of Chemistry and Chemical Engineering, Tianjin Key Laboratory of Organic Solar Cells and Photochemical Conversion, Tianjin University of Technology , 391 Binshui Xidao, Tianjin, Xiqing District, 300384, China.
authors.forename: Hongguang
authors.initials: H
authors.lastname: Lu
authors.affiliation: School of Chemistry and Chemical Engineering, Tianjin Key Laboratory of Organic Solar Cells and Photochemical Conversion, Tianjin University of Technology , 391 Binshui Xidao, Tianjin, Xiqing District, 300384, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Science, Tianjin University , 92 Weijin Road, Tianjin, Nankai District, 300072, China.
authors.forename: Zaifen
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Chemistry and Chemical Engineering, Tianjin Key Laboratory of Organic Solar Cells and Photochemical Conversion, Tianjin University of Technology , 391 Binshui Xidao, Tianjin, Xiqing District, 300384, China.
authors.forename: Jianbiao
authors.initials: J
authors.lastname: Ma
authors.affiliation: School of Chemistry and Chemical Engineering, Tianjin Key Laboratory of Organic Solar Cells and Photochemical Conversion, Tianjin University of Technology , 391 Binshui Xidao, Tianjin, Xiqing District, 300384, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
mesh_terms: D001391:Azo Compounds / Q000737:chemistry; D001692:Biological Transport; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D008823:Micelles; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D010084:Oxidation-Reduction; D055668:Photochemical Processes; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry
chemical_list: D001391:Azo Compounds; D004337:Drug Carriers; D008823:Micelles; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA; C009850:azobenzene