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

机译：探索基于阳离子脂质的非病毒载体的弛豫动力学：时间分辨荧光研究

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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).
机译：由阳离子二十八烷基二甲基溴化铵（DODAB）和中性的1-单油酰基-rac-甘油（MO）组成的脂质囊泡是有希望的非病毒核酸载体，可用于细胞内。其中，富含DODAB的囊泡比富含MO的囊泡显示出更高的细胞转染效率。这些混合脂质囊泡的结构松弛在其细胞转染效率中起关键作用，因为富含DODAB的囊泡的结构组织不同于富含MO的囊泡的结构组织。极化门控各向异性与新型荧光团6-乙酰基-（2-（（（4-羟基环己基）（甲基）氨基）萘）（ACYMAN）的皮秒分辨发射瞬态相结合，已被用于探测纯DODAB囊泡中的弛豫动力学，以及在MODA含量不同的DODAB混合囊泡中。在MO含量增加的混合脂质囊泡中，ACYMAN的取向弛豫和其局部环境的弛豫动力学都从0.2的摩尔分数（χ_（MO））到0.8的摩尔分数显着延迟，这与MO的刚性增加是一致的相对于富含DODAB的（χ_（MO）<0.5）囊泡，富含（χ_（MO）> 0.5）囊泡。因此，与先前在前文中观察到的相比，富含MO的囊泡（χ_（MO）> 0.5）更高的结构刚度导致它们的细胞转染效率低于更具柔韧性的富含DODAB的囊泡（χ_（MO）<0.5）。体内研究（Biochim。Biophys。Acta，Biomembr。，2014，1838，2555-2567）。

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