Versatile supramolecular pDNA vehicles via "click polymerization" of β-cyclodextrin with oligoethyleneamines
Versatile supramolecular pDNA vehicles via "click polymerization" of β-cyclodextrin with oligoethyleneamines
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DOI：
10.1016/j.biomaterials.2008.09.067
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发表时间：
2009-02-01
期刊：
影响因子：
14
通讯作者：
Reineke, Theresa M.
中科院分区：
文献类型：
--
作者：
Srinivasachari, Sathya;Reineke, Theresa M.
在这里，我们报道了高分子量聚合物(高达331 kDa)的高效合成，并检测了这些结构在培养的哺乳动物细胞中传递PDNA的能力。合成了两个系列的聚合物，一个是寡乙胺化学计量比不同的聚合物，CD1(46)、CD2(44)、CD3(49)和CD4(47)(分别位于重复单元中的1-4个寡乙胺，聚合度相似，n(W)=44-49)；另一个系列是随着聚合物长度的变化(重复单元中有四个乙烯胺)、CD4(27)、CD4(47)、CD4(93)和CD4(200)[n(W)=27、47、93、2001]。通过凝胶电泳、动态光散射和透射电子显微镜实验，这两个系列的聚合物都显示出有效的PDNA结合和致密化。DNA酶保护实验表明，随着聚合胺化学计量比的增加，PDNA的降解减少，其中聚合物CD3(49)和所有的CD4类似物在血清中完全保护PDNA长达8h。在HeLa细胞中检测了细胞摄取和基因表达谱，这类似地表明这两个系列的聚合物都具有高PDNA转移率，其中CD3(49)和CD4(93)具有最有效的荧光素酶基因表达。此外，所有结构的细胞存活率都很高。(C)2008爱思唯尔有限公司。保留所有权利。
Herein, we report the efficient synthesis of high molecular weight polymers (up to 331 kDa) that contain beta-cyclodextrin within the polymer backbone and the examination of these structures for pDNA delivery within cultured mammalian cells. Two series of polymers were synthesized, one with variation in oligoethyleneamine stoichiometry, Cd1(46), Cd2(44), Cd3(49), and Cd4(47) (1-4 oligoethyleneamines in the repeat unit, respectively and similar degree of polymerization, n(w)=44-49) and another with variation in polymer length (four ethyleneamines in the repeat unit), Cd4(27), Cd4(47), Cd4(93), and Cd4(200) [n(w) = 27, 47, 93, 2001 via the "click reaction". The two series of polymers revealed efficient pDNA binding and compaction through gel electrophoresis, dynamic light scattering, and transmission electron microscopy experiments. The DNase protection assay showed a decrease in pDNA degradation with an increase in the polymer amine stoichiometry, where polymer Cd3(49) and all of the Cd4 analogs completely protected pDNA for up to 8 h in serum. The cellular uptake and gene expression profiles were examined in HeLa cells, which similarly demonstrated that both the series of polymers had high pDNA delivery where, Cd3(49) and Cd4(93) had the most effective luciferase gene expression. In addition, the cell viability profiles were quite high with all of the structures. (C) 2008 Elsevier Ltd. All rights reserved.