Lipid-modified cell-penetrating peptide-based self-assembly micelles for co-delivery of narciclasine and siULK1 in hepatocellular carcinoma therapy

doi:10.1016/j.actbio.2018.05.030

CORC > 成都生物研究所 > 中国科学院成都生物研究所 > 食品安全与环境治理领域 > 应用与环境微生物研究

	Lipid-modified cell-penetrating peptide-based self-assembly micelles for co-delivery of narciclasine and siULK1 in hepatocellular carcinoma therapy
	Wang, Xiaoyun 2; Wu, Fengbo 2; Li, Guoyou 1; Zhang, Nan 2; Song, Xiangrong 2; Zheng, Yu 2; Gong, Changyang 2; Han, Bo 3; He, Gu 2
刊名	ACTA BIOMATERIALIA
	2018
卷号	74 页码:414-429
关键词	Hepatocellular carcinoma Narciclasine Cell penetrating peptide Codelivery Autophagy ULK1
ISSN号	1742-7061
DOI	10.1016/j.actbio.2018.05.030
产权排序	2
文献子类	Article
英文摘要	Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer, and one therapeutic approach is to target both the AMPK and autophagy pathways in order to synergistically promote programmed cell death. Here, a series of amphiphilic, lipid-modified cell-penetrating peptides were synthesized and allowed to self-assemble into micelles loaded with the AMPK activator narciclasine (Narc) and short interfering RNA targeting the unc-51-like kinase 1 (siULK1). The size of these micelles, their efficiency of transfection into cells, and their ability to release drug or siRNA cargo in vitro were pH-sensitive, such that drug release was facilitated in the acidic microenvironment of the tumor. Transfecting the micelles into HCC cells significantly inhibited protective autophagy within tumor cells, and delivering the micelles into mice carrying HCC xenografts induced apoptosis, slowed tumor growth, and inhibited autophagy. Our results indicate that co-delivering Narc and siULK1 in biocompatible micelles can safely inhibit tumor growth and protective autophagy, justifying further studies into this promising therapeutic approach against HCC. Statement of Significance We have focused on the targeted therapy of HCC via synergistically inhibiting the autophagy and inducing apoptosis. The lipid-modified cell-penetrating peptide can not only aggregate into micelles to load natural product narciclasine and ULK1 siRNA simultaneously, but also facilitate uptake and endosome escape with a pH-sensitive manner in HepG2 cells. HepG2 cell treated with siULK1-M-Narc has increased apoptotic levels and declined autophagy via the targeted regulation of AMPK-ULK1 signaling axis. The in vivo studies have confirmed that siULK1-M-Narc efficiently reduce the growth of tumor on HCC xenograft models with good safety. Thus, we suppose the lipid-modified cell-penetrating peptide has good application prospects in the targeted combinational therapy of HCC. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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WOS关键词	CANCER IN-VITRO ; AUTOPHAGY ; LIVER ; VIVO ; NANOPARTICLES ; APOPTOSIS ; PATHWAYS ; DEATH ; CHEMOTHERAPY ; DOXORUBICIN
WOS研究方向	Engineering ; Materials Science
语种	英语
出版者	ELSEVIER SCI LTD
WOS记录号	WOS:000437998200032
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/30688]
专题	环境治理与食品安全领域_应用与环境微生物研究
作者单位	1.Chinese Acad Sci, Chengdu Inst Biol, Chengdu 610065, Sichuan, Peoples R China; 2.Department of Pharmacy and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041,China; 3.Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Breeding Base Systemat Res Dev & Ut, Chengdu 611137, Sichuan, Peoples R China
推荐引用方式 GB/T 7714	Wang, Xiaoyun,Wu, Fengbo,Li, Guoyou,et al. Lipid-modified cell-penetrating peptide-based self-assembly micelles for co-delivery of narciclasine and siULK1 in hepatocellular carcinoma therapy[J]. ACTA BIOMATERIALIA,2018,74:414-429.
APA	Wang, Xiaoyun.,Wu, Fengbo.,Li, Guoyou.,Zhang, Nan.,Song, Xiangrong.,...&He, Gu.(2018).Lipid-modified cell-penetrating peptide-based self-assembly micelles for co-delivery of narciclasine and siULK1 in hepatocellular carcinoma therapy.ACTA BIOMATERIALIA,74,414-429.
MLA	Wang, Xiaoyun,et al."Lipid-modified cell-penetrating peptide-based self-assembly micelles for co-delivery of narciclasine and siULK1 in hepatocellular carcinoma therapy".ACTA BIOMATERIALIA 74(2018):414-429.