Bioreducible polymers as a determining factor for polyplex decomplexation rate and transfection.
Bioreducible polymers as a determining factor for polyplex decomplexation rate and transfection.
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DOI：
10.1021/bm301794d
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发表时间：
2013-02-11
影响因子：
6.2
通讯作者：
Bae YH
中科院分区：
文献类型：
--
作者：
Hwang HS;Kang HC;Bae YH
聚合物复合物的形成（复合）和基因从聚合物复合物中的释放（解复合）是聚合物基因递送中的主要事件，然而解复合速率对转染的影响很少被研究。本研究采用聚（L-赖氨酸）（PLL：MW ~7.4 kDa）和可还原PLL（RPLL）（MW ~6.7 kDa）的混合聚合物来设计解络合速率可控的PLL 100-xRPLLx/pDNA复合物（PRLx polyplexes）。模型基因（荧光素酶）在MCF 7和HEK 293细胞系中的转染效率随着PRLx复合物中x（RPLL含量）的增加而增加，直到分别在x=2.5和x=10时达到峰值，在此之后转染效率迅速下降。在MCF 7细胞中，PRL 2.5复合物产生的基因表达分别比PLL或RPLL复合物高3倍或223倍。类似地，PRL 10复合物转染的HEK 293细胞的转染效率分别是PLL或RPLL复合物的3.8倍或67倍。转染结果没有明显相关的粒径，表面电荷，络合/紧凑，细胞摄取，或细胞毒性的测试复合物。然而，解络合速率因聚合物中RPLL含量而异，这反过来又影响基因转染。通过PRLx聚合复合物递送的pDNA的核定位显示出与它们的转染效率类似的趋势。该研究表明，最佳解络合速率可导致pDNA的高核定位和转染。了解pDNA的解复合和细胞内定位可能有助于开发更有效的复合物。
Polyplex formation (complexation) and gene release from the polyplexes (decomplexation) are major events in polymeric gene delivery, however the effect of the decomplexation rate on transfection has been rarely investigated. This study employed mixed polymers of poly(L-lysine) (PLL: MW ~7.4 kDa) and reducible PLL (RPLL) (MW ~6.7 kDa) to design decomplexation rate-controllable PLL100-xRPLLx/pDNA complexes (PRLx polyplexes). The transfection efficiency of a model gene (luciferase) in MCF7 and HEK293 cell lines increased with increasing x (RPLL content) in the PRLx polyplexes until peaking at x=2.5 and x=10, respectively, after which point transfection efficiency declined rapidly. In MCF7 cells, PRL2.5 polyplex produced 3- or 223-fold higher gene expression than PLL or RPLL polyplexes, respectively. Similarly, the transfection efficiency of PRL10 polyplex-transfected HEK293 cells was 3.8- or 67-fold higher than that of PLL or RPLL polyplexes, respectively. The transfection results were not apparently related to the particle size, surface charge, complexation/compactness, cellular uptake, or cytotoxicity of the tested polyplexes. However, the decomplexation rate varied by RPLL content in the polyplexes, which in turn influenced the gene transfection. The nuclear localization of pDNA delivered by PRLx polyplexes showed a similar trend to their transfection efficiencies. This study suggests that an optimum decomplexation rate may result in high nuclear localization of pDNA and transfection. Understanding in decomplexation and intracellular localization of pDNA may help develop more effective polyplexes.
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影响因子：
14
作者：
Kang, Han Chang;Kang, Ho-Jung;Bae, You Han
通讯作者：
Bae, You Han
影响因子：
10.8
作者：
Manickam, Devika S.;Li, Jing;Putt, David A.;Zhou, Qing-Hui;Wu, Chao;Lash, Lawrence H.;Oupicky, David
通讯作者：
Oupicky, David
影响因子：
14
作者：
Kang, Han Chang;Bae, You Han
通讯作者：
Bae, You Han
DOI：
10.1016/j.jconrel.2012.06.036
发表时间：
2012-12-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Kang HC;Huh KM;Bae YH
通讯作者：
Bae YH
影响因子：
4.7
作者：
Jeong, Ji Hoon;Kim, Sun Hwa;Christensen, Lane V.;Feijen, Jan;Kim, Sung Wan
通讯作者：
Kim, Sung Wan