A structure–activity investigation of hemifluorinated bifunctional bolaamphiphiles designed for gene delivery

A new series of dissymmetric hemifluorocarbon bolaamphiphiles were designed to investigate their main characteristics as a non-viral gene transfer carrier. The dissymmetric functionalization of diiodoperfluorooctane led to bolaamphiphile molecules composed of a partially fluorocarbon core end-capped with a glycoside and an ammonium salt. The physical–chemical results, cytotoxic effect, gene complexation and transfection efficiency were analyzed and functional relationships were addressed. The study clearly showed that the chemical structure of bolaamphiphiles influences the complexation with DNA, gene transfer, and cytotoxicity. Two different polar head groups (histidine and lysine) have been tested for their efficiency to complex DNA. The impact of the side chain of bolaamphiphile on the interaction with DNA was also investigated. Good transfection activity was demonstrated for partially fluorinated bolaamphiphile having lysine head group. Weak cell cytotoxicity, positive surface charge of bolaplexes, well-defined structure, and protection from the DNAses seem to be essential characteristics for efficient transfection.

RésuméL'étude porte sur les potentialités d'une nouvelle série d'agents amphiphiles dissymétriques hémifluorocarbonés dans le domaine de la transfection de gènes. La dissymétrisation fonctionnelle du diiodoperfluorooctane a permis d'accéder à des structures bolaamphiphiles dotées d'un cœur fluorocarboné et de terminaisons de type saccharidique et ammonium. Les propriétés physico-chimiques, le type de structure supramoléculaire qu'ils forment en milieu aqueux, leur impact sur l'aptitude à la complexation et à la transfection de gènes de l'ensemble de ces structures ont été précisés. Une activité de transfection non négligeable a pu être observée pour les bolaamphiphiles partiellement fluorés et dotés de tête polaire cationique de type lysine.