title: PEG-based block catiomers possessing DNA anchoring and endosomal escaping functions to form polyplex micelles with improved stability and high transfection efficacy.
abstract: For the development of polyplex systems showing a high transfection efficacy without a large excess of polycations, a lysine (Lys) unit as a DNA anchoring moiety was introduced into the amino acid sequence in poly(ethylene glycol)-b-cationic poly(N-substituted asparagine) with a flanking N-(2-aminoethyl)-2-aminoethyl group (PEG-b-Asp(DET)) resulting in PEG-b-P[Lys/Asp(DET)], in which the Asp(DET) unit acts as a buffering moiety inducing endosomal escape with minimal cytotoxicity. PEG-b-P[Lys/Asp(DET)]/DNA polyplexes exhibited a narrow size distribution of approximately 90 nm without secondary aggregates at the stoichiometric N/P 1, suggesting the formation of PEG-shielded polyplex micelles. The introduction of Lys units into the catiomer sequence facilitated cellular uptake and a 100-fold higher level of gene expression with PEG-b-P[Lys/Asp(DET)]/DNA polyplex micelles prepared even at a lowered N/P 2, possibly due to the enhanced association power of the anchoring Lys units.
authors.affiliation: Department of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Kanjiro
authors.initials: K
authors.lastname: Miyata
authors.forename: Shigeto
authors.initials: S
authors.lastname: Fukushima
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D002412:Cations; D004247:DNA / Q000737:chemistry*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004355:Drug Stability; D011992:Endosomes / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008823:Micelles; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014162:Transfection
chemical_list: D002412:Cations; D004337:Drug Carriers; D008823:Micelles; D011092:Polyethylene Glycols; D004247:DNA; D008156:Luciferases