title: pH responsive PEGylation through metal affinity for gene delivery mediated by histidine-grafted polyethylenimine.
abstract: Polyethylene glycol (PEG) has been used to enhance the stability of a gene delivery system. The most commonly used approach is to add the PEG molecule by way of chemical conjugation. In this study, we prepared PEG-bearing nitrilotriacetic acid (ntaPEG) followed by chelation with either nickel or zinc ions. Polyethylenimine was grafted with histidine (hisPEI) and used as a primary gene carrier to form complexes with DNA. PEGylation was performed by incubating the complexes with chelated ntaPEG. It was noted that the coating of the chelated ntaPEG could provide a shielding effect against aggregation induced by bovine serum albumin and DNA release induced by heparin displacement, respectively. The coating was also found to improve cellular viability and maintain the transfection efficiency at a moderate level. The coated ntaPEG could dissociate from the complexes in an acidic condition of pH 4, suggesting that dePEGylation might occur in some acidic intracellular organelles, such as endosomes. This simple and effective PEGylation approach could be extended to other delivery systems to enhance the stability and to facilitate the dePEGylation process.
authors.affiliation: Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan. tsengwc@mail.ntust.edu.tw
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Tseng
authors.forename: Ling-Yu
authors.initials: LY
authors.lastname: Su
authors.forename: Tsuei-Yun
authors.initials: TY
authors.lastname: Fang
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D016466:CHO Cells; D002417:Cattle; D002614:Chelating Agents / Q000737:chemistry; D020099:Coated Materials, Biocompatible / Q000008:administration & dosage / Q000737:chemistry; D006224:Cricetinae; D003412:Cricetulus; D018014:Gene Transfer Techniques; D006639:Histidine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008422:Materials Testing; D009532:Nickel / Q000737:chemistry; D009571:Nitrilotriacetic Acid / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D014162:Transfection; D015032:Zinc / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D002614:Chelating Agents; D020099:Coated Materials, Biocompatible; D011092:Polyethylene Glycols; D006639:Histidine; D009532:Nickel; D011094:Polyethyleneimine; D015032:Zinc; D009571:Nitrilotriacetic Acid