Glucosylated polyethylenimine as a tumor-targeting gene carrier

Glucosylated polyethylenimine as a tumor-targeting gene carrier
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DOI:
10.1007/bf02978216
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发表时间:
2005-11-01
影响因子:
6.7
通讯作者:
Cho, CS
Cho, CS
中科院分区:
医学2区
文献类型:
--
作者:
Park, IK;Cook, SE;Cho, CS

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葡萄糖基化聚乙烯亚胺(GPEI)是通过促进肿瘤葡萄糖转运蛋白的糖代谢而合成的一种肿瘤靶向基因载体。GPEI/ DNA复合物的颗粒尺寸与GPEI的葡萄糖含量成比例地增加,而复合物的表面电荷不依赖于葡萄糖基化,部分原因是引入的短亲水基团的低效屏蔽。具有更高葡糖基化的GPEI(36 mol-%)即使在聚合物浓度高于200 μ g/mL时对细胞也没有细胞毒性作用。与未葡萄糖基化的PEI相比,葡萄糖基化诱导的转染效率降低小于一个数量级。GPEI/DNA复合物可能通过葡萄糖相关细胞受体与GPEI的葡萄糖部分特异性相互作用而转染肿瘤细胞。γ显像技术显示GPEI/DNA复合物分布于肝、脾和肿瘤组织中。
Glucosylated polyethylenimine (GPEI) was synthesized as a tumor-targeting gene carrier through facilitative glucose metabolism by tumor glucose transporter. Particle sizes of GPEI/ DNA complex increased in proportion to glucose content of GPEI, whereas surface charge of the complex was not dependent on glucosylation, partially due to inefficient shielding of the short hydrophilic group introduced. GPEI with higher glucosylation (36 mol-%) had no cytotoxic effect on cells even at polymer concentrations higher than 200 mu g/mL. Compared to unglucosylated PEI, glucosylation induced less than one-order decrease of transfection efficiency. Transfection of GPEI/DNA complex into tumor cells possibly occurred through specific interaction between glucose-related cell receptors and glucose moiety of GPEL Gamma imaging technique revealed GPEI/DNA complex was distributed in liver, spleen, and tumors.