NPC1L1-Targeted Cholesterol-Grafted Poly(beta-Amino Ester)/pDNA Complexes for Oral Gene Delivery

doi:10.1002/adhm.201800934

	NPC1L1-Targeted Cholesterol-Grafted Poly(beta-Amino Ester)/pDNA Complexes for Oral Gene Delivery
	Liu, Yuan 1,2; Chen, Dan 2; Li, Jialin 2,3; Xia, Dengning 2; Yu, Miaorong 2; Tao, Jinsong 2; Zhang, Xinxin 2; Li, Li 1; Gan, Yong 2
刊名	ADVANCED HEALTHCARE MATERIALS
	2019-04-01
卷号	8 期号:8 页码:12
关键词	cellular uptake cholesterol oral gene delivery transfection efficiency
ISSN号	2192-2640
DOI	10.1002/adhm.201800934
通讯作者	Gan, Yong(ygan@simm.ac.cn)
英文摘要	Gene vectors for oral delivery encounter harsh conditions throughout the gastrointestinal tract, and the continuous peristaltic activity can quickly remove the vectors, leading to inefficient intestinal permeation. Therefore, vectors have demanding property requirements, such as stability under various pH and, more importantly, efficient uptake in different intestinal segments. In this study, a functional polymer, cholesterol-grafted poly(beta-amino ester) (poly[hexamethylene diacrylate-beta-(5-amino-1-pentanol)] (CH-PHP)), is synthesized and electrostatically interacted with plasmid DNA to form a CH-PHP/DNA complex (CPNC). This complex is designed to target the Niemann-Pick C1-like receptor, a cholesterol receptor, to improve oral gene delivery efficacy. With the presence of cholesterol, CH-PHP shows mitigated cytotoxicity, enhanced enzyme resistance, and improved gene condensing ability. CPNC further contributes to approximate to 43.1- and 2.3-fold increases in luciferase expression in Caco-2 cells compared with PNC and Lipo 2000/DNA complexes, respectively. In addition, the in vivo transfection efficacy of CPNC is approximate to 4.1-, 2.1-, and 1.6-fold higher than that of Lipo 2000/DNA complexes in rat duodenum, jejunum, and ileum, respectively. Therefore, CPNC may be a promising delivery vector for gene delivery, and using a cholesterol-specific endocytic pathway can be a novel approach to achieve efficient oral gene transfection.
资助项目	National Natural Science Foundation of China[81573378] ; National Natural Science Foundation of China[81673379] ; National Natural Science Foundation of China[81773651] ; Pharmaceutical Innovation Project of Chinese Academy of Science[CASIMM01201016] ; K. C. Wong Education Foundation
WOS关键词	EZETIMIBE BLOCKS ; MESSENGER-RNA ; ALPHA SIRNA ; NANOPARTICLES ; NPC1L1 ; DNA ; PROTEIN ; COLON ; INTERNALIZATION ; TRANSFECTION
WOS研究方向	Engineering ; Science & Technology - Other Topics ; Materials Science
语种	英语
出版者	WILEY
WOS记录号	WOS:000468319500015
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/289746]
专题	中国科学院上海药物研究所
通讯作者	Gan, Yong
作者单位	1.Shanghai Univ, Dept Chem, Shanghai 200444, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China 3.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Liu, Yuan,Chen, Dan,Li, Jialin,et al. NPC1L1-Targeted Cholesterol-Grafted Poly(beta-Amino Ester)/pDNA Complexes for Oral Gene Delivery[J]. ADVANCED HEALTHCARE MATERIALS,2019,8(8):12.
APA	Liu, Yuan.,Chen, Dan.,Li, Jialin.,Xia, Dengning.,Yu, Miaorong.,...&Gan, Yong.(2019).NPC1L1-Targeted Cholesterol-Grafted Poly(beta-Amino Ester)/pDNA Complexes for Oral Gene Delivery.ADVANCED HEALTHCARE MATERIALS,8(8),12.
MLA	Liu, Yuan,et al."NPC1L1-Targeted Cholesterol-Grafted Poly(beta-Amino Ester)/pDNA Complexes for Oral Gene Delivery".ADVANCED HEALTHCARE MATERIALS 8.8(2019):12.