Enzyme-Activated Prodrug-Based Smart Liposomes Specifically Enhance Tumor Hemoperfusion with Efficient Drug Delivery to Pancreatic Cancer Cells and Stellate Cells

doi:10.1002/adfm.202100605

	Enzyme-Activated Prodrug-Based Smart Liposomes Specifically Enhance Tumor Hemoperfusion with Efficient Drug Delivery to Pancreatic Cancer Cells and Stellate Cells
	Duan, Nianxiu 1,2,3; Li, Junjun 2,4; Song, Sha 2,3; Wang, Feng 5; Yang, Yiwei 2; Nie, Di 2; Wang, Caifen 2; Sheng, Yingjie 2; Tao, Yali 1; Gao, Jie 1
刊名	ADVANCED FUNCTIONAL MATERIALS
	2021-08-11
页码	14
关键词	drug delivery pancreatic cancer prodrugs smart liposomes tumor-specific vascular promotion
ISSN号	1616-301X
DOI	10.1002/adfm.202100605
通讯作者	Xu, Can(xucan@smmu.edu.cn) ; Wei, Yan(ywei@shu.edu.cn)
英文摘要	Tumor-specific enhanced delivery of chemotherapeutics and modulators to tumor cells and activated pancreatic stellate cells (aPSCs), respectively, represents safer and more effective therapy for pancreatic cancer. Herein, a membrane type 1-matrix metalloproteinase (MT1-MMP)-cleavable spacer is used to assemble low-density cRGDfK onto thermosensitive liposomes loaded with phosphorylated calcipotriol (PCAL) and doxorubicin (DOX), yielding MR-T-PD. The liposome-linked cRGDfK prodrug on MR-T-PD surface is first activated by MT1-MMP, which is selectively expressed on tumor endothelial cells, to release cRGDfK. The free cRGDfK specifically promotes tumor angiogenesis, leading to 3.4-fold higher accumulation and a wider distribution of MR-T-PD in tumors. Furthermore, MR-T-PD rapidly releases PCAL and DOX into the interstitium under heat treatment. The released DOX enters tumor cells to induce apoptosis, whereas the PCAL prodrug is converted to CAL by alkaline phosphatase on the surface of aPSCs; CAL can then enter aPSCs to induce quiescence and promote the antitumor effect of DOX. Finally, by enhancing the exposure of DOX and CAL to tumor cells and aPSCs, respectively, in a tumor-specific manner, MR-T-PD exerts superior efficacy (a 5.9-fold decrease in tumor weight) without causing additional side effects. Overall, this prodrug-based smart liposome system represents a promising paradigm for pancreatic cancer therapy.
资助项目	National Natural Science Foundation of China[81872428] ; National Natural Science Foundation of China[81703010] ; National Natural Science Foundation of China[81372673] ; National Natural Science Foundation of China[82072051] ; China Postdoctoral Science Foundation[2016M600342]
WOS关键词	STRATEGIES ; THERAPY ; GROWTH ; ANGIOGENESIS ; INHIBITION ; INTEGRIN ; EFFICACY ; OVERCOME ; DESIGN
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000684032500001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/298104]
专题	中国科学院上海药物研究所
通讯作者	Xu, Can; Wei, Yan
作者单位	1.Shanghai Univ, Inst Translat Med, 99 Shangda Rd, Shanghai 200011, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China 3.Nanchang Univ, Dept Pharm, Med Coll, 461 Bayi Rd, Nanchang 330006, Jiangxi, Peoples R China 4.Univ Sci & Technol China, Nano Sci & Technol Inst, 166 Renai Rd, Suzhou 215123, Peoples R China 5.Shanghai Hansoh Biomed R&D Inc, Dept Med Chem, 3728 Jinke Rd, Shanghai 201203, Peoples R China 6.Changhai Hosp, Dept Gastroenterol, 168 Changhai Rd, Shanghai 200433, Peoples R China
推荐引用方式 GB/T 7714	Duan, Nianxiu,Li, Junjun,Song, Sha,et al. Enzyme-Activated Prodrug-Based Smart Liposomes Specifically Enhance Tumor Hemoperfusion with Efficient Drug Delivery to Pancreatic Cancer Cells and Stellate Cells[J]. ADVANCED FUNCTIONAL MATERIALS,2021:14.
APA	Duan, Nianxiu.,Li, Junjun.,Song, Sha.,Wang, Feng.,Yang, Yiwei.,...&Gan, Yong.(2021).Enzyme-Activated Prodrug-Based Smart Liposomes Specifically Enhance Tumor Hemoperfusion with Efficient Drug Delivery to Pancreatic Cancer Cells and Stellate Cells.ADVANCED FUNCTIONAL MATERIALS,14.
MLA	Duan, Nianxiu,et al."Enzyme-Activated Prodrug-Based Smart Liposomes Specifically Enhance Tumor Hemoperfusion with Efficient Drug Delivery to Pancreatic Cancer Cells and Stellate Cells".ADVANCED FUNCTIONAL MATERIALS (2021):14.