In vitro gene delivery mediated by lactosylated dendrimer (generation 3, G3)/α-cyclodextrin conjugates into hepatocytes

作者: Keiichi Motoyama , Yoshimasa Mori , Shogo Yamashita , Yuya Hayashi , Hirofumi Jono

DOI: 10.1007/S10847-010-9842-0

关键词:

摘要: The purpose of this study is to evaluate in vitro gene delivery efficiency polyamidoamine (PAMAM) starburst dendrimer (generation 3, G3) conjugates with α-cyclodextrin (α-CDE (G3)) bearing lactose (Lac-α-CDE) various degrees substitution the moiety (DSL) as a novel hepatocyte-selective carrier. Lac-α-CDE (G3, DSL 1.2) was found have much higher transfer activity than α-CDE (G3), (G2, 2.6) and Lac-α-CDEs 2.6, 4.1 6.1) HepG2 cells, which are dependent on expression cell-surface asialoglycoprotein receptor (ASGP-R). provided negligible cytotoxicity up charge ratio 100 (carrier/pDNA) cells. These results suggest potential use non-viral vector for toward hepatocytes.

参考文章(29)
Isabelle Fajac, Pascale Briand, Michel Monsigny, Gene therapy of cystic fibrosis: the glycofection approach. Glycoconjugate Journal. ,vol. 18, pp. 723- 729 ,(2001) , 10.1023/A:1020827507748
Maria A. Croyle, Blake J. Roessler, Cheng‐Pang Hsu, Rong Sun, Gordon L. Amidon, Beta cyclodextrins enhance adenoviral-mediated gene delivery to the intestine. Pharmaceutical Research. ,vol. 15, pp. 1348- 1355 ,(1998) , 10.1023/A:1011985101580
Eric Duverger, Valérie Carpentier, Annie-Claude Roche, Michel Monsigny, Sugar-dependent nuclear import of glycoconjugates from the cytosol. Experimental Cell Research. ,vol. 207, pp. 197- 201 ,(1993) , 10.1006/EXCR.1993.1181
Kaneto Uekama, Fumitoshi Hirayama, Tetsumi Irie, Cyclodextrin Drug Carrier Systems. Chemical Reviews. ,vol. 98, pp. 2045- 2076 ,(1998) , 10.1021/CR970025P
M. Thomas, A. M. Klibanov, Non-viral gene therapy: polycation-mediated DNA delivery Applied Microbiology and Biotechnology. ,vol. 62, pp. 27- 34 ,(2003) , 10.1007/S00253-003-1321-8
Hidetoshi Arima, Fumihiro Kihara, Fumitoshi Hirayama, Kaneto Uekama, Enhancement of gene expression by polyamidoamine dendrimer conjugates with α-, β-, and γ-cyclodextrins Bioconjugate Chemistry. ,vol. 12, pp. 476- 484 ,(2001) , 10.1021/BC000111N
Koki Wada, Hidetoshi Arima, Toshihito Tsutsumi, Fumitoshi Hirayama, Kaneto Uekama, Enhancing Effects of Galactosylated Dendrimer/α-Cyclodextrin Conjugates on Gene Transfer Efficiency Biological & Pharmaceutical Bulletin. ,vol. 28, pp. 500- 505 ,(2005) , 10.1248/BPB.28.500
Isabelle Fajac, Guiti Thévenot, Laurent Bédouet, Claire Danel, Marc Riquet, Marc Merten, Catherine Figarella, Josette Dall' Ava-Santucci, Michel Monsigny, Pascale Briand, Uptake of plasmid/glycosylated polymer complexes and gene transfer efficiency in differentiated airway epithelial cells. Journal of Gene Medicine. ,vol. 5, pp. 38- 48 ,(2003) , 10.1002/JGM.318
Janna C. Collins, Allan W. Wolkoff, Anatol G. Morell, Richard J. Stockert, Selective regulation of intrinsic membrane proteins in HepG2. Hepatology. ,vol. 8, pp. 108- 115 ,(1988) , 10.1002/HEP.1840080122
Koki Wada, Hidetoshi Arima, Toshihito Tsutsumi, Yuko Chihara, Kenjiro Hattori, Fumitoshi Hirayama, Kaneto Uekama, Improvement of gene delivery mediated by mannosylated dendrimer/α-cyclodextrin conjugates Journal of Controlled Release. ,vol. 104, pp. 397- 413 ,(2005) , 10.1016/J.JCONREL.2005.02.016