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  • Title: PEG-based block catiomers possessing DNA anchoring and endosomal escaping functions to form polyplex micelles with improved stability and high transfection efficacy.
    Author: Miyata K, Fukushima S, Nishiyama N, Yamasaki Y, Kataoka K.
    Journal: J Control Release; 2007 Oct 08; 122(3):252-60. PubMed ID: 17643543.
    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.
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