NDLI: Cationic gemini lipids containing polyoxyethylene spacers as improved transfecting agents of plasmid DNA in cancer cells

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Journal of Materials Chemistry B Vol - 2 Issue - 19

Journal of Materials Chemistry B Vol - 2 Issue - 9

Journal of Materials Chemistry B Vol - 2 Issue - 8

Journal of Materials Chemistry B Vol - 2 Issue - 7

Journal of Materials Chemistry B Vol - 2 Issue - 6

Journal of Materials Chemistry B Vol - 2 Issue - 5

Journal of Materials Chemistry B Vol -1

Cationic gemini lipids containing polyoxyethylene spacers as improved transfecting agents of plasmid DNA in cancer cells

Content Provider	Royal Society of Chemistry (RSC)
Author	Barrán-Berdón, Ana L. Datta, Sougata Bhattacharya, Santanu Kondaiah, Paturu Muñoz-Úbeda, Mónica Junquera, Elena Aicart, Emilio Misra, Santosh K.
Copyright Year	2014
Abstract	Lipoplex nano-aggregates have been analyzed through biophysical characterization (electrostatics, structure, size and morphology), and biological studies (transfection efficiency and cell viability) in five cancer cell lines. Lipoplexes were prepared from pEGFP-C3 plasmid DNA (pDNA) and mixed liposomes, constituted by a zwitterionic lipid (DOPE) and a gemini cationic lipid (GCL) synthesized in this work, [bis(hexadecyl dimethyl ammonium) oxyethylene], referred to as (C16Am)2(C2O)n, (where n is the oxyethylene spacer length, n = 1, 2 or 3, between the ammonium heads). Cryo-TEM micrographs show nano-aggregates with two multilamellar structures, a cluster-type (at low-to-medium GCL composition) and a fingerprint-type that coexists with the cluster-type at medium GCL composition and appears alone at high GCL composition. SAXS diffractograms show that these lipoplexes present three lamellar structures, two of them coexisting at low and high GCL composition. The optimized transfection efficiency (TE) of pDNA was higher for lipoplexes containing GCLs with a longer (n = 3) or shorter (n = 1) polyoxyethylene spacer, at high GCL composition (α = 0.7) with low charge ratio (ρeff = 2). In the all cancer cell lines studied, the TE of the optimized formulations was much better than those of both lipofectamine 2000 and lipoplexes with GCLs of the bis(hexadecyl dimethyl ammonium) alkane series recently reported. Probably, (a) the coexistence of two lamellar structures at high GCL composition synergizes the TE of these lipid vectors, (b) the orientation of the polyoxyethylene region in (C16Am)2(C2O)3/DOPE may occur in such a way that the spacing between two cationic heads becomes smaller than that in (C16Am)2(C2O)2/DOPE which is poor in terms of TE, and (c) the synergistic interactions between serum proteins and (C16Am)2(C2O)n/DOPE-pDNA lipoplexes containing a polyoxyethylene spacer improve TE, especially at high GCL content. Lipoplexes studied here show very low levels of toxicity, which confirm them as improved vectors of pDNA in gene therapy.
Starting Page	4640
Ending Page	4652
Page Count	13
File Format	HTM / HTML PDF
ISSN	2050750X
Volume Number	2
Issue Number	29
Journal	Journal of Materials Chemistry B
DOI	10.1039/c4tb00389f
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Electrostatics Transfection Cancer Plasmid DNA Lipid Project Gemini Ammonium Small-angle X-ray scattering Polyethylene glycol Gene therapy
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Materials Science Biomedical Engineering

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Cationic gemini lipids containing polyoxyethylene spacers as improved transfecting agents of plasmid DNA in cancer cells.

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Cationic gemini lipids containing polyoxyethylene spacers as improved transfecting agents of plasmid DNA in cancer cells

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