MT1-MMP-Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy

doi:10.1002/advs.201902746

	MT1-MMP-Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy
	Wei, Yan 1; Song, Sha 2; Duan, Nianxiu 2; Wang, Feng 3; Wang, Yuxi 1; Yang, Yiwei 1; Peng, Chengyuan 4; Li, Junjun 1; Nie, Di 1; Zhang, Xinxin 1
刊名	ADVANCED SCIENCE
	2020-07-10
页码	14
关键词	membrane type 1-matrix metalloproteinase-activated cilengitide pancreatic cancer smart liposomes vascular promotion
DOI	10.1002/advs.201902746
通讯作者	Gan, Yong(ygan@simm.ac.cn)
英文摘要	Promoting tumor angiogenesis effectively and specifically to resolve tumor-associated hypoperfusion holds promise for improving pancreatic cancer therapy. Herein, a doxorubicin (DOX) loaded smart liposome, MC-T-DOX, is constructed, that carries appropriately low-density cilengitide, an alpha v beta 3 integrin-specific Arg-Gly-Asp (RGD)-mimetic cyclic peptide, via a membrane type 1-matrix metalloproteinase (MT1-MMP) cleavable peptide. After being administered systemically in a hypoperfused pancreatic cancer mouse model at a low dose of cilengitide, the proangiogenic activity of MC-T-DOX is specifically "turned on" in tumor vessels through cleavage by MT1-MMP on tumor endothelial cells to release cilengitide. This locally released cilengitide increases tumor blood perfusion, thereby improving the accumulation and distribution of MC-T-DOX in the tumor site. The loaded-DOX then displays enhanced penetration and increased cellular uptake upon heat-triggered release from MC-T-DOX in the tumor interstitium, contributing to the improved tumor therapy efficacy. Therefore, the strategy of combining the modulation of tumor vascular promotion with smart nanodrug delivery represents a promising approach to improving drug delivery and therapeutic efficacy in a wide range of hypoperfused tumors.
资助项目	National Natural Science Foundation of China[81703010] ; National Natural Science Foundation of China[81872428] ; China Postdoctoral Science Foundation[2016M600342] ; National Key Research and Development Program of China[NBHY-2017-J1-3] ; Strategic Priority Research Program of Chinese Academy of Sciences[XDA15014200]
WOS关键词	INTEGRIN ALPHA(V)BETA(3) ; ANGIOGENESIS ; EFFICACY ; INHIBITION ; STRATEGIES ; BARRIERS ; DESIGN ; GROWTH
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science
语种	英语
出版者	WILEY
WOS记录号	WOS:000546679400001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/291892]
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.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Nanchang Univ, Coll Med, Dept Pharm, Nanchang 330066, Jiangxi, Peoples R China 3.Shanghai Hansoh Biomed R&D Inc, Dept Med Chem, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wei, Yan,Song, Sha,Duan, Nianxiu,et al. MT1-MMP-Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy[J]. ADVANCED SCIENCE,2020:14.
APA	Wei, Yan.,Song, Sha.,Duan, Nianxiu.,Wang, Feng.,Wang, Yuxi.,...&Gan, Yong.(2020).MT1-MMP-Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy.ADVANCED SCIENCE,14.
MLA	Wei, Yan,et al."MT1-MMP-Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy".ADVANCED SCIENCE (2020):14.