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Open AccessArticle

A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical Study

1
Grupo de Química Coloidal y Supramolecular, Departamento de Química Física, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, Spain
2
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
3
Dpto. Tecnología Química y Tensioactivos, IQAC-CSIC, 08034 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Nanomaterials 2018, 8(12), 1061; https://doi.org/10.3390/nano8121061
Received: 15 November 2018 / Revised: 10 December 2018 / Accepted: 12 December 2018 / Published: 16 December 2018
This work reports the synthesis of a novel gemini cationic lipid that incorporates two histidine-type head groups (C3(C16His)2). Mixed with a helper lipid 1,2-dioleoyl-sn-glycero-3-phosphatidyl ethanol amine (DOPE), it was used to transfect three different types of plasmid DNA: one encoding the green fluorescence protein (pEGFP-C3), one encoding a luciferase (pCMV-Luc), and a therapeutic anti-tumoral agent encoding interleukin-12 (pCMV-IL12). Complementary biophysical experiments (zeta potential, gel electrophoresis, small-angle X-ray scattering (SAXS), and fluorescence anisotropy) and biological studies (FACS, luminometry, and cytotoxicity) of these C3(C16His)2/DOPE-pDNA lipoplexes provided vast insight into their outcomes as gene carriers. They were found to efficiently compact and protect pDNA against DNase I degradation by forming nanoaggregates of 120–290 nm in size, which were further characterized as very fluidic lamellar structures based in a sandwich-type phase, with alternating layers of mixed lipids and an aqueous monolayer where the pDNA and counterions are located. The optimum formulations of these nanoaggregates were able to transfect the pDNAs into COS-7 and HeLa cells with high cell viability, comparable or superior to that of the standard Lipo2000*. The vast amount of information collected from the in vitro studies points to this histidine-based lipid nanocarrier as a potentially interesting candidate for future in vivo studies investigating specific gene therapies. View Full-Text
Keywords: lipid-based gene nanocarrier; gemini cationic lipid with histidine residues; gene delivery; plasmid DNAs; transfection; cell viability; biophysical characterization lipid-based gene nanocarrier; gemini cationic lipid with histidine residues; gene delivery; plasmid DNAs; transfection; cell viability; biophysical characterization
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MDPI and ACS Style

Martínez-Negro, M.; Blanco-Fernández, L.; Tentori, P.M.; Pérez, L.; Pinazo, A.; Tros de Ilarduya, C.; Aicart, E.; Junquera, E. A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical Study. Nanomaterials 2018, 8, 1061.

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