Bioconjugate Chemistry p. 2110 - 2118 (2010)
Update date:2022-08-03
Topics:
Jain, Namrata
Arntz, Youri
Goldschmidt, Valérie
Duportail, Guy
Mély, Yves
Klymchenko, Andrey S.
The success in gene therapy relies strongly on new efficient gene delivery vectors. Nonviral vectors based on lipids and polymers constitute an important alternative to the viral vectors. However, the key problem with these vectors is the poor structural control of their DNA complexes. In the present work, following new design we synthesized unsymmetrical bolaamphiphiles, molecules bearing neutral sugar (gluconic acid) and dicationic ornithine head groups connected by different long hydrophobic spacers. Within this design, a positively charged headgroup is expected to bind DNA, the hydrophobic spacer is to drive the formation of a monolayer membrane shell around DNA, while the neutral group is to be exposed outside of the complex. Our fluorescence and gel electrophoresis data showed that self-assembly of bolas and their interaction with DNA depend strongly on the bola structure. The size of bola/DNA complexes (bolaplexes) estimated from dynamic light scattering data was ~100 nm at low N/P (cationic nitrogen/DNA phosphate molar ratio), while at higher N/Ps it was significantly larger due to neutralization of their surface charge. Atomic force microscopy studies revealed nanostructural rod-shaped or spherical morphology of the bolaplexes. Transfection efficiency of the bolaplexes in vitro was significant when either DOPE or chloroquine were used as helping agents, suggesting that the key barrier for their internalization is the endosomal escape. Finally, all bolas showed low cytotoxicity (cell viability >80%). The present results show that bolas are prospective candidates for construction of nonviral gene delivery vectors. We believe that further optimization of polar head groups and a hydrophobic spacer in the bolas will lead to vectors with controlled small size and high transfection efficiency.
View MoreTaixing Shenfeng Chemical Co., Ltd.
Contact:+86-523-87117033, 87117666
Address:4# Yinsanlu, Huangqiao town, Taixing, Jiangsu, China.
SuZhou Bichal Biological Technology CO.,LTD
Contact:+86-512-68051130
Address:NO.32 huoju road HI-TECH Industrial development zone SuZhou China
website:http://www.finetechnology-ind.com
Contact:86-27-87465837
Address:wuhan
website:http://www.joyochem.com
Contact:0531-82687558, 0531-82687326
Address:Factory Building 11, Jinan Comprehensive free trade zone, Shandong, China
Shanghai Demand Chemical Co., ltd,China
Contact:86-021-55237578/55239122
Address:Room 3H, No.578, Yingkou Road, Yangpu District, Shanghai, China
Doi:10.1021/ml1001807
(2011)Doi:10.1016/0022-328X(81)80013-7
(1989)Doi:10.1007/s11172-009-0320-z
(2009)Doi:10.1021/om1006837
(2010)Doi:10.1021/acs.joc.9b00095
(2019)Doi:10.1016/j.tetasy.2010.07.030
(2010)