一种具有高核定位能力的胍基化生物还原聚合物，可用于基因传递系统。
A guanidinylated bioreducible polymer with high nuclear localization ability for gene delivery systems.
机构信息
Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
出版信息
Biomaterials. 2010 Mar;31(7):1798-804. doi: 10.1016/j.biomaterials.2009.10.034. Epub 2009 Oct 24.
Abstract
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 even at a weight ratio of 20 in reducing condition (2.5mm DTT) due to their biodegradation. GBP also could construct 200 nm-sized and positively charged (approximately 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.
摘要
胍基化生物可还原聚合物（GBP）被开发用于基因传递系统，利用胍基的细胞穿透能力。GBP 可以在琼脂糖凝胶电泳中完全阻止 pDNA 的重量比为 5，但在还原条件（2.5mM DTT）下，即使重量比为 20，pDNA 也会从 GBP 聚合物中释放出来，这是由于它们的生物降解。GBP 还可以与 pDNA 构建 200nm 大小的正电荷（约 30mV）聚合物纳米颗粒。研究发现，GBP 的细胞毒性最小，与支架聚合物聚（半胱氨酸双丙烯酰胺-二氨基己烷）（poly（CBA-DAH））相比，GBP 的转染效率提高了约 8 倍，甚至比在哺乳动物细胞系中 PEI25k 的转染效率更高。由于生物可还原聚合物和胍基的结构优势，其具有高细胞摄取效率（96.1%）和强的 pDNA 递送至细胞核的能力，这也表明 GBP 是一种很有前途的高效基因传递系统候选物。
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