Folate-Equipped Nanolipoplexes Mediated Efficient Gene Transfer into Human Epithelial Cells

International Journal of Molecular Sciences

Emmanuel Mornet¹  Nathalie Carmoy¹  Céline Lainé³  Lo໼ Lemiègre³  Tony Le Gall¹  Isabelle Laurent³  Remi Marianowski²  Claude Férec¹  Pierre Lehn¹  Thierry Benvegnu³ 

[1] INSERM U1078, IFR 148 ScInBIoS, Université de Bretagne Occidentale, 46 rue Félix Le Dantec, CS 51819, 29218 Brest Cedex 2, France; E-Mails:;Service d’ORL et de chirurgie cervico-faciale, CHU de BREST hôpital Morvan, 2 avenue du maréchal Foch 29609 Brest, France; E-Mail:;Ecole Nationale Supérieure de Chimie de Rennes, CNRS, UMR 6226, Avenue du Général Leclerc, CS 50837, 35708 Rennes Cedex 7, France; E-Mails:

关键词: cystic fibrosis;    cationic lipids;    neutral lipid nanocomplexes;    folic acid;    folate receptors;    epithelial cells;   

DOI  :  10.3390/ijms14011477

来源: mdpi

【 摘 要 】

Since recombinant viral vectors have been associated with serious side effects, such as immunogenicity and oncogenicity, synthetic delivery systems represent a realistic alternative for achieving efficacy in gene therapy. A major challenge for non-viral nanocarriers is the optimization of transgene expression in the targeted cells. This goal can be achieved by fine-tuning the chemical carriers and the adding specific motifs to promote cellular penetration. Our study focuses on the development of novel folate-based complexes that contain varying quantities of folate motifs. After controlling for their physical properties, neutral folate-modified lipid formulations were compared in vitro to lipoplexes leading to comparable expression levels. In addition, no cytotoxicity was detected, unlike what was observed in the cationic controls. Mechanistically, the delivery of the transgene appeared to be, in part, due to endocytosis mediated by folate receptor targeting. This mechanism was further validated by the observation that adding free folate into the medium decreased luciferase expression by 50%. In vivo transfection with the folate-modified MM18 lipid, containing the highest amount of FA-PEG₅₇₀-diether co-lipid (w:w; 90:10), at a neutral charge ratio, gave luciferase transgene expression. These studies indicate that modification of lipids with folate residues could enhance non-toxic, cell-specific gene delivery.

【 授权许可】

CC BY   
© 2013 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.