A guanidinylated bioreducible polymer with high nuclear localization ability for gene delivery systems.
A guanidinylated bioreducible polymer with high nuclear localization ability for gene delivery systems.
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DOI：
10.1016/j.biomaterials.2009.10.034
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发表时间：
2010-03
期刊：
影响因子：
14
通讯作者：
Kim, Sung Wan
中科院分区：
文献类型：
--
作者：
Kim, Tae-il;Lee, Minhyung;Kim, Sung Wan
胍基化生物可还原聚合物（GBP）是利用胍基的细胞穿透能力开发的基因传递系统。在琼脂糖凝胶电泳中，GBP可以完全阻止pDNA的重量比为5，但由于它们的生物降解，pDNA在还原条件下（2.5 mM DTT）从GBP复合物中释放出来。GBP还可以与pDNA构建200 nm大小和带正电荷（~30 mV）的聚合物纳米颗粒。GBP的细胞毒性被发现是最小的，并且GBP显示出比支架聚合物聚（胱胺双丙烯酰胺-二氨基己烷）（聚（CBA-DAH））提高约8倍的转染效率，并且在哺乳动物细胞系中甚至比PEI 25 k更高的转染效率。由于生物可还原聚合物和胍基的结构优势，其高细胞摄取效率（96.1%）和对pDNA递送的强核定位能力也被鉴定，表明GBP是有效基因递送系统的有希望的候选者。
Guanidinylated bioreducible polymer (GBP) was developed for gene delivery systems utilizing cellular penetrating ability of guanidine groups. GBP could retard pDNA from a weight ratio of 5 completely in agarose gel electrophoresis but pDNA was released from GBP polyplexes in reducing condition (2.5 mM DTT) due to their biodegradation. GBP also could construct 200 nm-sized and positively charged (~30 mV) polyplex nanoparticles with pDNA. The cytotoxicity of GBP was found to be minimal and GBP showed about 8 folds improved transfection efficiency than a scaffold polymer, poly(cystaminebisacrylamide-diaminohexane) (poly(CBA-DAH)) and even higher transfection efficiency than PEI25k in mammalian cell lines. Its high cellular uptake efficiency (96.1 %) and strong nuclear localization ability for pDNA delivery due to the structural advantage of bioreducible polymer and guanidine groups were also identified, suggesting GBP is a promising candidate for efficient gene delivery systems.
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