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探索基于阳离子脂质的非病毒载体的弛豫动力学:一项时间分辨荧光研究。

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

作者信息

Singh Priya, Mukherjee Dipanjan, Singha Subhankar, Sharma V K, Althagafi Ismail I, Ahmed Saleh A, Mukhopadhyay R, Das Ranjan, Pal Samir Kumar

机构信息

Department of Chemical, Biological & Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences Block JD, Sector III, Salt Lake Kolkata 700106 India

Centre of Health Science &Technology, JIS Institute of Advanced Studies Kolkata India.

出版信息

RSC Adv. 2019 Nov 1;9(61):35549-35558. doi: 10.1039/c9ra06824d. eCollection 2019 Oct 31.

DOI:10.1039/c9ra06824d
PMID:35528090
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9074709/
Abstract

Lipid vesicles composed of cationic dioctadecyldimethylammonium bromide (DODAB) and neutral 1-monooleoyl--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 ( ) of 0.2 to that of 0.8 which is consistent with increased rigidity of the MO-rich ( > 0.5) vesicles relative to the DODAB-rich ( < 0.5) vesicles. Therefore, higher structural rigidity of the MO-rich vesicles ( > 0.5) gives rise to their lower cell transfection efficiency than the more flexible DODAB-rich ( < 0.5) vesicles as observed in previous studies (, 2014, , 2555-2567).

摘要

由阳离子二辛基二甲基溴化铵(DODAB)和中性1-单油酰基甘油(MO)组成的脂质囊泡是很有前景的非病毒核酸载体,可用于将核酸递送至细胞。其中,富含DODAB的囊泡比富含MO的囊泡表现出更高的细胞转染效率。这些混合脂质囊泡的结构弛豫在其细胞转染效率中起关键作用,因为富含DODAB的囊泡的结构组织与富含MO的囊泡不同。结合新型荧光团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的偏振门控各向异性已被用于探测纯DODAB囊泡以及含有不同MO含量的DODAB混合囊泡中的弛豫动力学。随着MO含量从摩尔分数(χ)0.2增加到0.8,ACYMAN的取向弛豫及其局部环境的弛豫动力学在混合脂质囊泡中均显著延迟,这与富含MO(χ>0.5)的囊泡相对于富含DODAB(χ<0.5)的囊泡刚性增加是一致的。因此,如先前研究(,2014,,2555 - 2567)中所观察到的,富含MO(χ>0.5)的囊泡较高的结构刚性导致其细胞转染效率低于更具柔韧性的富含DODAB(χ<0.5)的囊泡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/e44ecf96736a/c9ra06824d-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/49957fad1d86/c9ra06824d-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/4f5d6e883ece/c9ra06824d-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/b272e820717b/c9ra06824d-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/0a0f69216259/c9ra06824d-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/3365f5ad3c80/c9ra06824d-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/fdeb6112b6a8/c9ra06824d-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/98767e42c1d5/c9ra06824d-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/f7ffddbec35e/c9ra06824d-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/e44ecf96736a/c9ra06824d-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/49957fad1d86/c9ra06824d-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/4f5d6e883ece/c9ra06824d-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/b272e820717b/c9ra06824d-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/0a0f69216259/c9ra06824d-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/3365f5ad3c80/c9ra06824d-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/fdeb6112b6a8/c9ra06824d-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/98767e42c1d5/c9ra06824d-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/f7ffddbec35e/c9ra06824d-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d113/9074709/e44ecf96736a/c9ra06824d-f8.jpg

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