Highly efficient in vivo gene transfection by plasmid/PEI complexes coated by anionic PEG derivatives bearing carboxyl groups and RGD peptide
Highly efficient in vivo gene transfection by plasmid/PEI complexes coated by anionic PEG derivatives bearing carboxyl groups and RGD peptide
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DOI：
10.1016/j.biopha.2007.12.009
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发表时间：
2008-09-01
影响因子：
7.5
通讯作者：
Koyama, Yoshiyuki
中科院分区：
文献类型：
--
作者：
Sakae, Mitsuko;Ito, Tomoko;Koyama, Yoshiyuki
合成了一种新型的阴离子聚乙二醇衍生物PEG-Suc，它含有17.7对羧酸侧链。PEG-Suc沉积在DNA/聚乙烯亚胺复合物上，即使在高剂量比下也不破坏它们。用PEG-Suc包被的DNA复合物使其表面重新充电，并有效地保护它们免受白蛋白诱导的聚集。侧链中成对的羧基表现出更高的质子海绵效应。带负电荷的表面会降低复合物与细胞的静电结合，对培养细胞的转染效率不高。然后引入RGD肽侧链作为恶性细胞表面的配体以补偿降低的电粘附。RGD-PEG-Suc包被的质粒/PEI复合物对培养的B16细胞的报告蛋白活性提高了3倍以上。这些生物相容性DNA复合物与配体注射到小鼠尾静脉后，在肿瘤、肺和肝中获得了非常高的基因表达。(C)2007年，Elsevier Masson SAS。All rights reserved.
A new class of an anionic poly (ethylene glycol) derivative, PEG-Suc, bearing 17.7 pairs of carboxylic acid-side chains was synthesized. PEG-Suc deposited onto the DNA/polyethyleneimine complexes without destroying them even at high dose ratio. Coating of the DNA complexes by PEG-Suc recharged their surface to negative, and effectively protected them from the albumin-induced aggregation. Paired carboxyl groups in the side chains showed higher proton sponge effect. Negatively charged surface would diminish the electrostatic binding of the complexes to the cells, and the transfection efficiency on the cultured cells was not high. RGD peptide side chain as a ligand to malignant cell surfaces was then introduced to compensate the reduced electrical adhesion. RGD-PEG-Suc-coated plasmid/PEI complex brought about more than 3 times higher reporter protein activity on the cultured B16 cells. Those bio-compatible DNA complexes with ligand attained very high gene expression in tumor, lung, and liver after injection into mouse tail vein. (C) 2007 Elsevier Masson SAS. All rights reserved.