期刊
SENSORS
卷 9, 期 8, 页码 6346-6361出版社
MDPI
DOI: 10.3390/s90806346
关键词
cyclodextrin; PAMAM dendrimer; carrier; DNA; siRNA; shRNA
资金
- Japan Society for the Promotion of Science [16590114, 18590144, 20590037]
- Grants-in-Aid for Scientific Research [20590037, 18590144, 16590114] Funding Source: KAKEN
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 alpha-CyD having an average degree of substitution (DS) of 2.4 [alpha-CDE (G3, DS2)] displayed remarkable properties as DNA, shRNA and siRNA delivery carriers through the sensor function of alpha-CDEs toward nucleic acid drugs, cell surface and endosomal membranes. In an attempt to develop cell-specific gene transfer carriers, we prepared sugar-appended alpha-CDEs. Of the various sugar-appended.-CDEs prepared, galactose-or mannose-appended alpha-CDEs provided superior gene transfer activity to alpha-CDE in various cells, but not cell-specific gene delivery ability. However, lactose-appended alpha-CDE [Lac-alpha-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 alpha-CDE [Fol-P alpha C (G3)] and revealed that Fol-P alpha C (G3) imparted folate receptor (FR)-mediated cancer cell-selective gene transfer activity. Consequently, alpha-CDEs bearing integrated, multifunctional molecules may possess the potential to be novel carriers for DNA, shRNA and siRNA.
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