Cationic core-shell liponanoparticles for ocular gene delivery

doi:10.1016/j.biomaterials.2012.06.079

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	Cationic core-shell liponanoparticles for ocular gene delivery
	Jiang, Min 1,2; Gan, Li 2; Zhu, Chunliu2 ; Dong, Yang 2; Liu, Jianping 1; Gan, Yong2
刊名	BIOMATERIALS
	2012-10
卷号	33 期号:30 页码:7621-7630
关键词	Core-shell Cationic lipids Chitosan nanoparticles Endocytosis pathway Lysosome Transfection
ISSN号	0142-9612
DOI	10.1016/j.biomaterials.2012.06.079
文献子类	Article
英文摘要	To achieve enhanced gene transfection efficiency with ocular eye-drop therapy, a cationic core shell liponanoparticle (DLCS-NP) was designed by enveloping the plasmid-laden chitosan nanoparticle (CS-NP) into a cationic lipid shell. The cellular uptake of DLCS-NP was up to 1.25-fold and 5-fold higher than that of CS-NP and lipid-coated chitosan nanoparticles (LCS-NP), respectively. Further endocytosis inhibition investigation discovered that facilitated by the cationic outer lipid layer, several other distinct pathways (besides clathrin-mediated endocytosis) were involved in the endocytosis of DLCS-NP. Endolysosome trafficking experiment verified that cationic lipid coating could facilitate the endolysosome escape of DLCS-NP. Consequently, using enhanced green fluorescence protein (EGFP) as a reporter gene, DLCS-NP-treated human conjunctival epithelial cells exhibited 3.1- and 3.5-fold more intense EGFP expression than that of LCS-NP and CS-NP, respectively. Finally, in vivo transfection experiments on rabbits revealed that EGFP expression exhibited 2.52-fold increase in DLCS-NP group than that of CS-NP group. In summary, this type of cationic core-shell liponanoparticle, possessing multiple functions including better DNA protecting effect, superior cellular uptake efficiency, utilization of multiple endocytic pathways, and endolysosome escaping ability, may represent a promising strategy for ocular gene (C) 2012 Elsevier Ltd. All rights reserved.
资助项目	Natural Sciences Foundation of Shanghai China[11ZR1444700] ; National Natural Sciences Foundation of China[81102387] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09301-001] ; National Basic Research Program of China[2009CB930300]
WOS关键词	IN-VITRO ; CHITOSAN NANOPARTICLES ; CELLULAR UPTAKE ; DRUG-DELIVERY ; TRANSFECTION EFFICIENCY ; SIRNA DELIVERY ; CELLS ; COMPLEXES ; SURFACE ; LIPOSOMES
WOS研究方向	Engineering ; Materials Science
语种	英语
出版者	ELSEVIER SCI LTD
WOS记录号	WOS:000308524000031
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277929]
专题	药物制剂研究中心药物化学研究室
通讯作者	Gan, Yong
作者单位	1.China Pharmaceut Univ, Sch Pharm, Nanjing 210009, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Materia Med, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Jiang, Min,Gan, Li,Zhu, Chunliu,et al. Cationic core-shell liponanoparticles for ocular gene delivery[J]. BIOMATERIALS,2012,33(30):7621-7630.
APA	Jiang, Min,Gan, Li,Zhu, Chunliu,Dong, Yang,Liu, Jianping,&Gan, Yong.(2012).Cationic core-shell liponanoparticles for ocular gene delivery.BIOMATERIALS,33(30),7621-7630.
MLA	Jiang, Min,et al."Cationic core-shell liponanoparticles for ocular gene delivery".BIOMATERIALS 33.30(2012):7621-7630.