Lactose-ornithine bolaamphiphiles for efficient gene delivery in vitro.
The development of new nonviral vectors characterized by high transfection efficiency and low cytotoxicity remains an important challenge in the field of gene delivery. Unsymmetrical bolaamphiphiles (bolas) appear as new emerging candidates for this application. In this work, new unsymmetrical bolas, bearing neutral lactonic acid and cationic ornithine residues at the two ends of a hydrophobic spacer, were synthesized and their properties were compared to analogues bearing a gluconic acid residue. The new bolas showed DNA binding and condensation at higher N/P ratios than their gluconic analogues, probably due to their larger neutral head group. Whereas the size of the complexes of the new bolas with DNA (bolaplexes) increased with N/P, as a result of charge neutralization, their formulations with DOPE at high N/P were of small size (ca. 200 nm). These DOPE formulations showed high transfection efficiency in different cell lines (HeLa, COS-7 and HepG2), close to that of jetPEI. Their cytotoxicity was relatively low, which allowed repetitive transfection in vitro. Fluorescence imaging showed that the bolaplexes bind rapidly to cell surface and internalize mainly through endocytosis. This work suggests a new type of efficient nonviral vectors based on bolaamphiphiles.
Laboratoire de Biophotonique et Pharmacologie, UMR 7213 CNRS, Université de Strasbourg, Faculté de Pharmacie, 74, Route du Rhin, 67401 ILLKIRCH Cedex, France.
Namrata
N
Jain
Valérie
V
Goldschmidt
Sule
S
Oncul
Youri
Y
Arntz
Guy
G
Duportail
Yves
Y
Mély
Andrey S
AS
Klymchenko
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004705:Endocytosis; D005663:Furans / Q000737:chemistry* / Q000633:toxicity; D005942:Gluconates / Q000737:chemistry; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007785:Lactose / Q000031:analogs & derivatives / Q000737:chemistry* / Q000633:toxicity; D008856:Microscopy, Fluorescence; D036103:Nanotechnology; D009952:Ornithine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011728:Pyridones / Q000737:chemistry* / Q000633:toxicity; D013501:Surface-Active Agents / Q000737:chemistry* / Q000633:toxicity; D013997:Time Factors; D014162:Transfection / Q000379:methods*
D005663:Furans; D005942:Gluconates; D010714:Phosphatidylethanolamines; D011728:Pyridones; D013501:Surface-Active Agents; C543575:bolaamphiphile; D004247:DNA; D009952:Ornithine; D007785:Lactose; C030691:gluconic acid