Probing relaxation dynamics of a cationic lipid based non-viral carrier: a time-resolved fluorescence study

Abstract

Lipid vesicles composed of cationic dioctadecyldimethylammonium bromide (DODAB) and neutral 1-monooleoyl-rac-glycerol (MO) are promising non-viral carriers of nucleic acids for delivery into cells. Among them, higher cell transfection efficiency was displayed by DODAB-rich vesicles than those enriched with MO. Structural relaxation of these mixed lipid vesicles plays a key role in their cell transfection efficiency because structural organization of the DODAB-rich vesicles are different from that of the MO-rich vesicles. Polarization-gated anisotropy in conjunction with picosecond resolved emission transients of a novel fluorophore 6-acetyl-(2-((4-hydroxycyclohexyl)(methyl)amino)naphthalene) (ACYMAN) has been employed to probe relaxation dynamics in pure DODAB vesicles, and in mixed vesicles of DODAB with varying content of MO. Both orientational relaxation of ACYMAN and relaxation dynamics of its local environment are retarded significantly in mixed lipid vesicles with increasing MO content, from a mole fraction (χ_MO) of 0.2 to that of 0.8 which is consistent with increased rigidity of the MO-rich (χ_MO > 0.5) vesicles relative to the DODAB-rich (χ_MO < 0.5) vesicles. Therefore, higher structural rigidity of the MO-rich vesicles (χ_MO > 0.5) gives rise to their lower cell transfection efficiency than the more flexible DODAB-rich (χ_MO < 0.5) vesicles as observed in previous in vivo studies (Biochim. Biophys. Acta, Biomembr., 2014, 1838, 2555–2567).