包含β-环糊精、聚乙烯亚胺和 5-氟-2'-脱氧尿苷的双功能缀合物，用于药物输送和基因转染。

Bifunctional conjugates comprising β-cyclodextrin, polyethylenimine, and 5-fluoro-2'- deoxyuridine for drug delivery and gene transfer.

机构信息

Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou, China.

出版信息

Bioconjug Chem. 2010 Oct 20;21(10):1855-63. doi: 10.1021/bc1002136.

PMID:20853891

Abstract

Earlier reports indicated that the conjugates (PEI(600)-CD, PC) of β-cyclodextrin and low-molecular-weight polyethylenimine (PEI, M(w) 600) can be used as efficient gene carriers in glioma cancer therapy. Incorporating anticancer drugs onto PC conjugates may endow them with new and interesting properties for great applications. In this work, FU-PEI(600)-CD (FPC) conjugates comprising PC and 5-fluoro-2'-deoxyuridine (FdUrd) were prepared as new bifunctional anticancer prodrugs with improved therapeutic effects, as well as good gene transfer efficiency. In comparison with free FdUrd, FPC could inhibit proliferation and enhance cytotoxicity on glioma cells. The results of hematoxylin and eosin (HE) staining indicated that C6 cells treated with FPC shrunk more seriously. Unlike FdUrd, cell cycle analysis indicated that C6 cells were primarily arrested in the G1 phase in the presence of FPC. Cellular uptake of FPC in C6 cells was about 10 times higher than that of FdUrd. In addition, the in vitro and in vivo gene transfection indicated that FPC still exhibited good gene expression efficiency. With the ability to deliver drugs and transfer genes, such bifunctional FPC conjugates may have great potential applications in combination therapy of cancers.

摘要

早期的报告表明，β-环糊精和低分子量聚乙烯亚胺（PEI，Mw 600）的缀合物（PEI（600）-CD，PC）可用作神经胶质瘤癌症治疗中的有效基因载体。将抗癌药物结合到 PC 缀合物上可能会赋予它们新的有趣性质，从而具有广泛的应用前景。在这项工作中，包含 PC 和 5-氟-2'-脱氧尿苷（FdUrd）的 FU-PEI（600）-CD（FPC）缀合物被制备为具有改善的治疗效果以及良好的基因转导效率的新型双功能抗癌前药。与游离 FdUrd 相比，FPC 能够抑制神经胶质瘤细胞的增殖并增强其细胞毒性。苏木精和伊红（HE）染色的结果表明，用 FPC 处理的 C6 细胞收缩得更严重。与 FdUrd 不同，细胞周期分析表明，在存在 FPC 的情况下，C6 细胞主要被阻滞在 G1 期。FPC 在 C6 细胞中的摄取量约是 FdUrd 的 10 倍。此外，体外和体内基因转染表明 FPC 仍表现出良好的基因表达效率。这种具有双重功能的 FPC 缀合物具有递药和转染基因的能力，在癌症的联合治疗中可能具有巨大的应用潜力。