Arginine-conjugated polypropylenimine dendrimer as a non-toxic and efficient gene delivery carrier

Arginine-conjugated polypropylenimine dendrimer as a non-toxic and efficient gene delivery carrier
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DOI:
10.1016/j.biomaterials.2006.12.013
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发表时间:
2007-04-01
期刊:
影响因子:
14
通讯作者:
Park, Jong-sang
Park, Jong-sang
中科院分区:
工程技术1区
文献类型:
--
作者:
Kim, Tae-il;Baek, Jung-un;Park, Jong-sang

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我们合成了用于基因传递系统的精氨酸缀合的聚丙烯亚胺树枝状聚合物 G2 (DAB-8)、PPI2-R。合成的PPI2R可以在重量比为4时完全阻滞质粒DNA,并且通过PicoGreen试剂检测,PPI2-R复合物在电荷比为2时显示出小于10%的荧光,表明其具有良好的DNA凝聚能力。在电荷比为 150 时,PPI2-R 聚合复合物的尺寸测量为约 200 nm。PPI2-R 即使在 150 μg/mL 浓度下也显示出 80-90% 的细胞活力。发现 PPI2-R 的转染效率与 PEI25kD 相当,比未修饰的 PPI2 在 HeLa 和 293 细胞上的转染效率高 8-214 倍。此外,由于 PPI2-R 对 HeLa 细胞的细胞毒性较低,因此用 10 μg pDNA 处理时,PPI2-R 的转染效率比 PE125kD 高 4 倍。最后,PPI2-R 在 HUVEC 上的转染效率比 PE125kD 高 2-3 倍,显示出其作为原代细胞基因递送载体的潜力。这些结果表明,精氨酸缀合PPI2成功地开发了低毒性和高转染效率的基因递送载体。 (c) 2006 Elsevier Ltd. 保留所有权利。
We synthesized arginine-conjugated polypropylenimine dendrimer G2 (DAB-8), PPI2-R for gene delivery systems. Synthesized PPI2R could retard plasmid DNA at a weight ratio of 4 completely and PPI2-R polyplexes showed a fluorescence of less than 10% over a charge ratio of 2 by PicoGreen reagent assay, suggesting its good DNA condensing ability. The size of PPI2-R polyplex was measured to about 200 nm at a charge ratio of 150. PPI2-R displayed 80-90% cell viability at even a 150 mu g/mL concentration. Transfection efficiency of PPI2-R was found to be high comparable to that of PEI25kD and to be 8-214 times higher than that of unmodified PPI2 on HeLa and 293 cells. Moreover, PPI2-R showed 4 times higher transfection efficiency than PE125kD, treating with 10 mu g pDNA because of its low cytotoxicity on HeLa cells. Finally, PPI2-R showed a transfection efficiency 2-3 times higher than PE125kD on HUVECs, showing its potency as a gene delivery carrier for primary cells. These results demonstrate that arginine-conjugation of PPI2 is successful in developing a low toxic and highly transfection efficient gene delivery carrier. (c) 2006 Elsevier Ltd. All rights reserved.