Recent Findings Concerning PAMAM Dendrimer Conjugates with Cyclodextrins as Carriers of DNA and RNA 英文参考文献.docVIP

Sensors 2009, 9, 6346-6361; doi:10.3390/OPEN ACCESS sensors ISSN 1424-8220 /journal/sensors Review Recent Findings Concerning PAMAM Dendrimer Conjugates with Cyclodextrins as Carriers of DNA and RNA Hidetoshi Arima * and Keiichi Motoyama Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan; E-Mail: motoyama@kumamoto-u.ac.jp (K.M.) * Author to whom correspondence should be addressed; E-Mail: arimah@gpo.kumamoto-u.ac.jp; Tel.: +81-96-371-4160; Fax: +81-96-371-4420 Received: 2 July 2009; in revised form: 6 August 2009 / Accepted: 7 August 2009 / Published: 17 August 2009 Abstract: We have evaluated the potential use of various polyamidoamine (PAMAM) dendrimer [dendrimer, generation (G) 2-4] conjugates with cyclodextrins (CyDs) as novel DNA and RNA carriers. Among the various dendrimer conjugates with CyDs, the dendrimer (G3) conjugate with ?-CyD having an average degree of substitution (DS) of 2.4 [?-CDE (G3, DS2)] displayed remarkable properties as DNA, shRNA and siRNA delivery carriers through the sensor function of ?-CDEs toward nucleic acid drugs, cell surface and endosomal membranes. In an attempt to develop cell-specific gene transfer carriers, we prepared sugar-appended ?-CDEs. Of the various sugar-appended ?-CDEs prepared, galactose- or mannose-appended ?-CDEs provided superior gene transfer activity to ?-CDE in various cells, but not cell-specific gene delivery ability. However, lactose-appended ?-CDE [Lac-?-CDE (G2)] was found to possess asialoglycoprotein receptor (AgpR)-mediated hepatocyte-selective gene transfer activity, both in vitro and in vivo. Most recently, we prepared folate-poly(ethylene glycol)-appended ?-CDE [Fol-P?C (G3)] and revealed that Fol-P?C (G3) imparted folate receptor (FR)-mediated cancer cell- selective gene transfer activity. Consequently, ?-CDEs bearing integrated, multifun