Chitosan N-betainates/DNA self-assembly nanoparticles for gene delivery: In vitro uptake and transfection efficiency
Chitosan N-betainates/DNA self-assembly nanoparticles for gene delivery: In vitro uptake and transfection efficiency
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用于基因传递的壳聚糖 N-甜菜酸盐/DNA 自组装纳米粒子：体外摄取和转染效率
DOI：
10.1016/j.ijpharm.2008.12.012
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发表时间：
2009-04-17
影响因子：
5.8
通讯作者：
Li, Yaping
中科院分区：
文献类型：
--
作者：
Gao, Yu;Zhang, Zhiwen;Li, Yaping
本工作的目的是研究N-甜菜碱壳聚糖(CSB)的甜菜碱取代度对CSB/DNA复合纳米粒(CsBns)对COS-7和MDA-MB-468细胞的摄取、细胞毒性和转染率的影响。三种取代度的聚合物(CsB12、CsB47和CsB85)与PDNA络合形成CsBN12s、CsBN47s和CsBN85s。与壳聚糖/PDNA复合纳米粒(CSNS)相比，在中性pH条件下，CsBns具有更小的粒径和更高的Zeta电位，对pH的依赖性更小。CsBN85的细胞摄取能力强于CsBN47和CsBN12。CsBns显示出比CSNS更高的细胞毒性，并且随着取代度的增加，其毒性有增加的趋势。COS-7细胞的转染率随取代度的增加而增加，而MDA-MB-468细胞的转染率则相反。经甜菜碱修饰后的壳聚糖对DNA的摄取能力增强，细胞毒作用增强，对细胞的转染率有一定的影响。增加CSB的甜菜碱取代量能提高复合纳米粒在COS-7细胞中的摄取和转染率，但随着甜菜碱替代量的增加，细胞对CSB的敏感性越高，细胞的细胞毒性越强，导致转染率降低。在两种细胞系中，细胞摄取或毒性在影响转染率方面的主要作用是不同的。这些结果为进一步开发壳聚糖衍生物/PDNA复合体作为非病毒基因载体提供了重要的指导。(C)2009年，爱思唯尔出版。
The aim of this work is to investigate the effect of betaine substitution degree of chitosan N-betainates (CsB) on cellular uptake, cytotoxicity and transfection efficiency of CsB/DNA complex nanoparticles (CsBNs) against COS-7 and MDA-MB-468 cells. The polymers with three substitution degrees (CsB12, CsB47 and CsB85) complexed with pDNA formed CsBN12s, CsBN47s and CsBN85s. The CsBNs showed less pH dependency with smaller particle size and higher zeta potential than that of chitosan/pDNA complex nanoparticles (CsNs) at neutral pH. CsBN85s showed stronger cellular uptake than that of CsBN47s or CsBN12s. CsBNs showed higher cytotoxicity than CsNs, and a trend increasing toxicity with substitution degree increasing. In COS-7 cells, the transfection efficiency increased with the substitution degree increasing, while the opposite result was observed in MDA-MB-468 cells. Chitosan modified with betaine could increase its ability to facilitate DNA uptake and its cytotoxicity, both of which showed the influence on transfection efficiency. It was able to increase cellular uptake and transfection efficiency of complex nanoparticles in COS-7 cells to increase betaine substitution of CsB, however, the higher sensitivity of MDA-MB-468 cells to CsBs led to decreased transfection efficiency due to the increased cytotoxicity with betaine substitution increasing. The predominant role of cellular uptake or toxicity in affecting transfection efficiency was different in two cell lines. These results provided an important guidepost for further development of chitosan derivatives/pDNA complexes as non-viral gene vectors. (C) 2009 Published by Elsevier B.V.