Dexamethasone-Conjugated Low Molecular Weight Polyethylenimine as a Nucleus-Targeting Lipopolymer Gene Carrier

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• 作者：Yun Mi Bae ; Hye Choi ; Seungah Lee ; Seong Ho Kang ; Young Tae Kim ; Kihoon Nam ; Jong Sang Park ; Minhyung Lee ; Joon Sig Choi
• 刊名：Bioconjugate Chemistry
• 出版年：2007
• 出版时间：November 2007
• 年：2007
• 卷：18
• 期：6
• 页码：2029 - 2036
• 全文大小：970K
• 年卷期：v.18,no.6(November 2007)
• ISSN：1520-4812

文摘

Dexamethasone, a glucocorticoid steroid, can dilate the nuclear pore complexes and translocate into the nucleus when it is bound to its glucocorticoid receptor, suggesting that the transport of DNA into the nucleus may be facilitated by the reagent. In this research, dexamethasone was conjugated to low molecular weight polyethylenimine (2kDa) for efficient translocation of the polymer/DNA complex into the nucleus. Polyethylenimine (PEI)–dexamethasone (PEI–Dexa) was synthesized by one-step reaction using the Traut’s reagent. In gel retardation assay, the PEI–Dexa/DNA complex was completely retarded at or above 0.3/1 weight ratio (polymer/DNA). The average size distributions and ζ-potential values of the complexes were measured at various weight ratios. In vitro transfection assay showed that the PEI–Dexa/DNA complex had higher gene delivery efficiency compared to PEI 2kDa/DNA complex. The localization of PEI–Dexa/plasmid DNA complexes in the nucleus was confirmed by using total internal reflection fluorescence and Nomarski differential interference contrast microscope as well as confocal microscope. Therefore, with efficient nuclear translocation and low cytotoxicity, PEI–Dexa may be useful for nonviral gene therapy.