Oligoamines grafted hyperbranched polyether as high efficient and serum-tolerant gene vectors.
Oligoamines grafted hyperbranched polyether as high efficient and serum-tolerant gene vectors.
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DOI：
10.1016/j.colsurfb.2013.07.017
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发表时间：
2013-11
期刊：
影响因子：
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通讯作者：
Yun‐Xia Sun;Bingqiao Yang;Si Chen;Qi Lei;Jun Feng;Xue-feng Qiu;N. Dong;R. Zhuo;Xianzheng Zhang
中科院分区：
文献类型：
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作者：
Yun‐Xia Sun;Bingqiao Yang;Si Chen;Qi Lei;Jun Feng;Xue-feng Qiu;N. Dong;R. Zhuo;Xianzheng Zhang
为了开发低毒、高效、耐血清多阳离子的基因传递系统，将三乙基四胺（TETA）和四乙基戊二胺（TEPA）等不同的低聚胺偶联到cooh功能化的多支聚（3-乙基-3-氧乙二烯乙醇）上，合成了一系列接枝高支聚醚的低聚胺-g- hbp。结果表明，低聚胺-g- hbp具有良好的缓冲能力、较强的DNA结合能力和较高的抗蛋白质吸附能力。体外细胞毒性测定表明，与25 kDa PEI相比，低聚胺-g- hbp具有更低的细胞毒性。在一定N/P比下，TEPA-g-HBP/DNA复合物的转染效率显著高于25 kDa PEI/DNA复合物。有趣的是，与25 kDa PEI相比，即使血清浓度增加到30%，TEPA-g-HBP的血清耐受能力也大大提高。激光共聚焦图像进一步显示，随着低聚胺-g- hbp中二级氨基乙烯基团数量的增加，细胞核中YOYO-1标记的DNA数量增加。低聚胺-g- hbp作为基因传递载体具有广阔的临床应用前景。
To develop low toxic, high efficient, and excellent serum-tolerant polycation gene delivery systems, a series of oligoamines grafted hyperbranched polyether (oligoamines-g-HBP) were synthesized by conjugating different oligoamines, including triethylenetetramine (TETA) and tetraethylenepentamine (TEPA), onto COOH-functionalized hyperbranched poly(3-ethyl-3-oxetanemethanol). It was found that oligoamines-g-HBP exhibited good buffering capacity, strong DNA binding and high resistance against protein adsorption.In vitrocytotoxicity measurement indicated that oligoamines-g-HBP had much lower cytotoxicity as compared with 25 kDa PEI. The transfection efficiency of TEPA-g-HBP/DNA complexes at a certain N/P ratio was significantly higher than that of 25 kDa PEI/DNA complexes. Interestingly, it was found that TEPA-g-HBP had much improved serum-tolerant capability as compared with 25 kDa PEI even when serum concentration was increased to 30%. Confocal laser images further showed that the amount of YOYO-1 labeled DNA in nuclei got increased with increasing the number of secondary amino ethylene groups in oligoamines-g-HBP. The oligoamines-g-HBP presented great potential as gene delivery vectors for further clinical applications.