Altering amine basicities in biodegradable branched polycationic polymers for nonviral gene delivery.
Altering amine basicities in biodegradable branched polycationic polymers for nonviral gene delivery.
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DOI：
10.1021/bm901147k
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发表时间：
2010-03-08
影响因子：
6.2
通讯作者：
Mikos, Antonios G.
中科院分区：
文献类型：
--
作者：
Chew, Sue Anne;Hacker, Michael C.;Saraf, Anita;Raphael, Robert M.;Kasper, F. Kurtis;Mikos, Antonios G.
本工作以不同的胺单体和三元丙烯酸酯单体三羟甲基丙烷三丙烯酸酯为原料，通过Michael加成反应合成了可生物降解的支化聚阳离子聚合物。这些聚合物在不同的pH范围内解离的胺的数量不同，这被认为对基因传递过程的不同部分有利。P-DED是由三羟甲基丙烷三丙烯酸酯和二甲基乙二胺合成的聚合物，在所有合成的聚合物中，当pH为7.4时，可用于PDNA络合的质子化胺的数量最多。与其他聚合物相比，P-DED在聚合物/质粒DNA(PDNA)质量比为10：1时形成了正向多聚体(13.9±0.5 mV)，只有在较高质量比时才形成正向多聚体。用流式细胞仪检测，在最高聚合物/PDNA重量比(300：1)下合成的聚合物形成的多聚体中，增强型绿色荧光蛋白报告基因的转染率(5.3±1.0%至30.6±6.6%)高于裸露的PDNA(0.8±0.4%)。P-DED(重量比300：1)形成的复合体的转染率(30.6±6.6%)也高于支化聚乙烯亚胺(重量比2：1，25.5±2.7%)形成的复合体。这项研究的结果表明，在pH 7.4以上离解的胺类聚合物可以作为正电荷基团在pH 7.4时与PDNA络合，可以合成出稳定的聚合物，具有更高的Zeta电位和更小的流体动力学尺寸，从而有效地转染细胞。这项工作表明，利用不同的胺单体可以合成具有不同缓冲能力的含有不同胺官能团的聚合物，并将其用作有效的基因传递载体。
In this work, biodegradable branched polycationic polymers were synthesized by Michael addition polymerization from different amine monomers and the triacrylate monomer trimethylolpropane triacrylate. The polymers varied in the amount of amines that dissociate in different pH ranges, which are considered to be beneficial to different parts of the gene delivery process. P-DED, a polymer synthesized from trimethylolpropane triacrylate and dimethylethylenediamine, had the highest number of protonated amines that are available for pDNA complexation at pH 7.4 of all polymers synthesized. P-DED formed a positive polyplex (13.9 ± 0.5 mV) at a polymer/plasmid DNA (pDNA) weight ratio of 10:1 in contrast to the other polymers synthesized, which formed positive polyplexes only at higher weight ratios. Polyplexes formed with the synthesized polymers at the highest polymer/pDNA weight ratio tested (300:1) resulted in higher transfection with enhanced green fluorescent protein reporter gene (5.3 ± 1.0% to 30.6 ± 6.6%) compared to naked pDNA (0.8 ± 0.4%), as quantified by flow cytometry. Polyplexes formed with P-DED (weight ratio of 300:1) also showed higher transfection (30.6 ± 6.6%) as compared to polyplexes formed with branched polyethylenimine (weight ratio of 2:1, 25.5 ± 2.7%). The results from this study demonstrated that polymers with amines that dissociate above pH 7.4, which are available as positively charged groups for pDNA complexation at pH 7.4, can be synthesized to produce stable polyplexes with increased zeta potential and decreased hydrodynamic size that efficiently transfect cells. This work indicated that polymers containing varying amine functionalities with different buffering capabilities can be synthesized by using different amine monomers and used as effective gene delivery vectors.
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