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Issue 41, 2017, Issue in Progress
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Scaling the effect of hydrophobic chain length on gene transfer properties of di-alkyl, di-hydroxy ethylammonium chloride based cationic amphiphiles

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Abstract

The success of gene therapy critically depends on the availability of efficient transfection vectors. Cationic lipids are the most widely studied non-viral vectors. The molecular architecture of the cationic lipid determines its transfection efficiency. Variations in alkyl chain lengths of lipids influence self-assembly and liposomal fusion with the cell membrane. These factors determine the transfection ability of the lipid. Thus, to probe the effect of asymmetry in hydrophobic chains on transfection efficiency, we designed and synthesized a series of cationic lipids by systematically varying one of the two alkyl chains linked to the quaternary nitrogen centre from C18 to C10 and keeping the other alkyl C18 chain constant (Lip1818-Lip1810). Transfection studies in multiple cultured mammalian cells (CHO, B16F10 and HeLa) revealed that the lipids with C18:C14 and C18:C12 alkyl chains (Lip1814 & Lip1812) showed 20–30% higher transfection efficacies than their counterparts at 2 : 1 and 4 : 1 lipid to pDNA charge ratios. Cryo-transmission electron images showed unilamellar vesicle structures for the liposomes of lipids. Mechanistic studies involving Small Angle X-ray Scattering (SAXS) revealed that asymmetry in the hydrophobic region has a significant impact on liposomal fusion with the plasma membrane model. Collectively, these findings demonstrate that chain length asymmetry in the hydrophobic region of cationic lipids has an important role in their liposome–DNA interactions at optimal 2 : 1 and 4 : 1 lipid to pDNA charge ratios, which in turn modulates their gene transfer properties.

Graphical abstract: Scaling the effect of hydrophobic chain length on gene transfer properties of di-alkyl, di-hydroxy ethylammonium chloride based cationic amphiphiles

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Supplementary files

Article information


Submitted
23 Feb 2017
Accepted
28 Apr 2017
First published
11 May 2017

This article is Open Access

RSC Adv., 2017,7, 25398-25405
Article type
Paper

Scaling the effect of hydrophobic chain length on gene transfer properties of di-alkyl, di-hydroxy ethylammonium chloride based cationic amphiphiles

A. A. Hiwale, C. Voshavar, P. Dharmalingam, A. Dhayani, R. Mukthavaram, R. Nadella, O. Sunnapu, S. Gandhi, V. G. M. Naidu, A. Chaudhuri, S. Marepally and P. K. Vemula, RSC Adv., 2017, 7, 25398
DOI: 10.1039/C7RA02271A

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