Stabilization of cancer-specific gene carrier via hydrophobic interaction for a clear-cut response to cancer signaling.
Stabilization of cancer-specific gene carrier via hydrophobic interaction for a clear-cut response to cancer signaling.
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DOI：
10.1016/j.jconrel.2013.06.011
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发表时间：
2013-09
期刊：
影响因子：
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通讯作者：
Chan Woo Kim;R. Toita;Jeong-Hun Kang;Kai Li;Eun Kyung Lee;G. Zhao;Daiki Funamoto;T. Nobori;Yuta Nakamura;Takeshi Mori;T. Niidome;Y. Katayama
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文献类型：
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作者：
Chan Woo Kim;R. Toita;Jeong-Hun Kang;Kai Li;Eun Kyung Lee;G. Zhao;Daiki Funamoto;T. Nobori;Yuta Nakamura;Takeshi Mori;T. Niidome;Y. Katayama
在这里，我们开发了一种新的基因载体，包括线性聚乙烯亚胺（LPEI）接枝与疏水改性的阳离子肽含有长烷基链，用于癌症特异性基因传递。阳离子肽是蛋白激酶Cα（PKCα）的底物，已知PKC α在癌细胞中特异性活化。疏水修饰的LPEI-C10-peptide可通过阴离子DNA链与阳离子肽底物之间的静电和疏水相互作用与DNA形成复合物。肽的疏水修饰不影响肽对PKCα的反应性，而复合物显示出改善的细胞内摄取。由于有效的内体逃逸和增强的稳定性，该复合物显著改善了转基因对细胞内PKCα活性的调节。
Here, we developed a new gene carrier, comprising a linear polyethylenimine (LPEI) grafted with a hydrophobically modified cationic peptide containing a long alkyl chain, for use in cancer-specific gene delivery. The cationic peptide is a substrate of protein kinase Cα (PKCα), which is known to be activated specifically in cancer cells. The hydrophobically modified LPEI-peptide conjugate (LPEI-C10-peptide) could form a polyplex with DNA through electrostatic and hydrophobic interactions between the anionic DNA strands and the cationic peptide substrate. The hydrophobic modification of the peptide did not affect the reactivity of the peptide toward PKCα, while the polyplex showed improved intracellular uptake. Because of the efficient endosomal escape and enhanced stability, the polyplex significantly improved the transgene regulation responding to intracellular PKCα activity.