Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
Curr Top Med Chem. 2014;14(4):465-77. doi: 10.2174/1568026613666131219123610.
Recently, various cyclodextrin (CyD)-grafted polymers and supramolecules have been developed as gene and oligonucleotide carriers. We have demonstrated that among the various polyamidoamine starburst(TM) dendrimers (dendrimers) conjugates with CyDs (CDEs), the dendrimer (G2 or G3) conjugate with α-CyD showed high gene and oligonucleotide transfer activity with negligible cytotoxicity. In addition, to develop tissue- or cell-specific gene transfer carriers, we also prepared α-CDEs modified with functional molecules, such as mannose, fucose, galactose, lactose, polyethylene glycol (PEG) and folate-PEG. Moreover, polypseudorotaxane-appended α-CDEs were developed as sustained release systems for DNA and siRNA. Interestingly, glucronylglucosyl-β-CyD conjugates with dendrimer (G2) (GUG-β-CDE (G2)) showed high gene transfer activity compared to α-CDE (G2) and β-CDE (G2). In this review, we focus on the potential use of various CDEs as DNA and oligonucleotide transfer carriers.
最近，各种环糊精（CyD）接枝聚合物和超分子已被开发为基因和寡核苷酸载体。我们已经证明，在各种聚酰胺胺星型（TM）树枝状大分子（树枝状大分子）与 CyD（CDEs）的缀合物中，与α-CyD 缀合的树枝状大分子（G2 或 G3）表现出高基因和寡核苷酸转移活性，而细胞毒性可忽略不计。此外，为了开发组织或细胞特异性基因转导载体，我们还制备了用功能分子（如甘露糖、岩藻糖、半乳糖、乳糖、聚乙二醇（PEG）和叶酸-PEG）修饰的α-CDE。此外，还开发了带有聚伪轮烷的α-CDE 作为 DNA 和 siRNA 的缓释系统。有趣的是，与树枝状大分子（G2）（GUG-β-CDE（G2））缀合的葡糖醛基葡萄糖基-β-CyD 与α-CDE（G2）和β-CDE（G2）相比，表现出高基因转移活性。在这篇综述中，我们重点介绍了各种 CDE 作为 DNA 和寡核苷酸转导载体的潜在用途。
