title: Sugar-appended polyamidoamine dendrimer conjugates with cyclodextrins as cell-specific non-viral vectors.
abstract: The widespread use of various cyclodextrin (CyD)-appended polymers and polyrotaxanes as gene carriers has been reported. Among the various polyamidoamine dendrimer (dendrimer) conjugates with CyDs (CDE), the dendrimer (G3) conjugate with α-CyD having an average degree of substitution (DS) of 2.4 (α-CDE (G3, DS 2)) displayed remarkable properties as DNA carriers. In an attempt to develop cell-specific gene transfer carriers, we prepared some sugar-appended α-CDEs, e.g. mannosylated, galactosylated, and lactosylated α-CDEs. In addition, PEGylated Lac-α-CDEs (G3) were prepared and evaluated as a hepatocyte-selective and serum-resistant gene transfer carrier. Moreover, PEGylated-α-CDE/CyD polypseudorotaxane systems for novel sustained DNA release system have been developed. Interestingly, glucronylglucosyl-β-cyclodextrin (GUG-β-CyD) conjugates with dendrimer (G2) (GUG-β-CDE (G2)) had superior gene transfer activity to α-CDE (G2), expecting a development of new series of sugar-appended CDEs over α-CDEs (G2). Collectively, sugar-appended α-CDEs have the potential as novel cell-specific and safe carriers for DNA.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. Electronic address: arimah@gpo.kumamoto-u.ac.jp.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Arima
authors.forename: Keiichi
authors.initials: K
authors.lastname: Motoyama
authors.forename: Taishi
authors.initials: T
authors.lastname: Higashi
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D002241:Carbohydrates / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry*; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry*; D018014:Gene Transfer Techniques; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans
chemical_list: D002241:Carbohydrates; D003505:Cyclodextrins; D050091:Dendrimers; C104700:PAMAM Starburst; D004247:DNA
keywords: ASGPR; ATTR; BSA; CDP; CyDs; Cyclodextrin; DNA; FR; Fuc-R; Gal-α-CDE; GalNAc; Gene delivery; GlcNAc; Glucronylglucosyl-β-cyclodextrin; LPS; MR; N-acetyl-d-glucosamine; N-acetylgalactosamine; PAMAM; PEI; PLL; Polyamidoamine dendrimer; TTR; amyloidogenic transthyretin; asialoglycoprotein receptor; bovine serum albumin; cyclodextrins; dendrimer conjugates with α-CyD; folate receptor; fucose receptor; galactose-appended α-CDE; lipopolysaccharide; mannose receptor; pDNA; plasmid pDNA; poly-l-lysine; polyamidoamine; polyethyleneimine; polypseudorotaxane; transthyretin; α-CDEs; α-CyD; α-cyclodextrin; β-CyD; β-CyD-containing polycations; β-cyclodextrin