Dimerizable Redox-Sensitive Triazine-Based Cationic Lipids for in vitro Gene Delivery

Autor: Marco Folini, Chiara Verpelli, Carlo Sala, Gabriele Candiani, Walter Panzeri, Fiorenza Viani, Massimo Frigerio, Matteo Zanda, Monica Sani, Luca Chiamenti, Nadia Zaffaroni
Rok vydání: 2007
Předmět:
Zdroj: ChemMedChem
2 (2007): 292–296. doi:10.1002/jgm.1186
info:cnr-pdr/source/autori:Candiani G., Frigerio M., Viani F., Verpelli C., Sala C., Chiamenti L., Zaffaroni N., Folini M., Sani M., Panzeri W., Zanda M./titolo:Dimerizable redox-sensitive triazine-based cationic lipids for in vitro gene delivery/doi:10.1002%2Fjgm.1186/rivista:ChemMedChem (Print)/anno:2007/pagina_da:292/pagina_a:296/intervallo_pagine:292–296/volume:2
ISSN: 1860-7187
1860-7179
DOI: 10.1002/cmdc.200600267
Popis: Background: Despite the use of currently optimized lipofection conditions, including transfection in serum-depleted media, the efficiency of gene transfer is low and high transfection rates often induce cytotoxicity. A lipid formulation with transfection efficiency not inhibited by serum would provide an advance towards in vivo applications. Methods: We explored the ability of the cationic lipid SH-14 to dimerize upon DNA and form lipoplexes, and potentially release nucleic acids in the intracellular reducing milieu. We investigated the critical micelle-forming concentration of SH-14 and its intrinsic toxicity, size and Zeta potential measurements, the in vitro cytotoxicity of SH-14/ plasmid DNA lipoplexes and their ability to transfect cells. Results: Among all the charge ratios (CR, +/-) tested, lipoplexes at CR 10 with a mean diameter of 295 nm and a surface charge of +20 mV, exhibited the best compromise between transfection efficiency and tolerability. SH-14 presented the same cytotoxicity level whether alone or complexed in lipoplexes. Lipofections carried out in serum-free medium shared a transfection efficiency, on average, of 40% and a cytotoxicity of 38%. An increase of 73% in transfection efficiency and 24% in cell viability were obtained, extending lipofection over 48 h in complete-medium. Moreover, when serum concentration was increased from 10% to 50%, a three-fold increase in plasmid dose led to more than 72% of cells being transfected with almost no sign of cytotoxicity. Conclusions: Overall, SH-14 presents good potential as a novel transfection reagent to be used in the presence of serum.
Databáze: OpenAIRE
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