Tumor Cells-Selective Bionic Nanodevice Exploiting Heparanase Combats Metastatic Breast Cancer

doi:10.1002/adfm.201707289

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	Tumor Cells-Selective Bionic Nanodevice Exploiting Heparanase Combats Metastatic Breast Cancer
	Lang, Tianqun 1,2,3; Ran, Wei 1,2,3; Dong, Xinyue 2,3; Zheng, Zhong 2,3; Liu, Yiran 2,3; Yin, Qi2,3 ; Li, Yaping2,3
刊名	ADVANCED FUNCTIONAL MATERIALS
	2018-04-25
卷号	28 期号:17
关键词	breast cancer heparan sulfate metastasis red blood cell membranes tumor-targeting micelles
ISSN号	1616-301X
DOI	10.1002/adfm.201707289
文献子类	Article
英文摘要	The clinical application of the cytotoxic chemotherapeutic agents in the treatment of metastatic breast cancer is limited by their poor selectivity to cancer cells. In this work, a bionic nanodevice consisting of the docetaxel (DTX)-heparan sulfate (HS) conjugate (HS-DTX) micelle with a red blood cells membrane (RBC) coating on its surface, termed as rHS-DTX, is first constructed. It is found that the cytotoxicity of DTX is concealed by HS in human mammary epithelial Michigan Cancer Foundation (MCF)-10A cells but restored in human mammary cancer MCF-7 cells because HS is hydrolyzed by heparanase (Hpa), which is overexpressed only in MCF-7 but not MCF-10A cells. The RBC coating enhances the cellular uptake of HS-DTX and endows it with the long circulating ability in blood. In the MCF-7 metastatic breast cancer mice model, rHS-DTX exhibits 6.35-fold higher intratumor DTX accumulation than the free DTX injection and achieves a tumor inhibiting rate of 98.2% and a lung metastasis suppression rate of 99.6%. No severe toxicity is observed in the major organs and blood of mice treated with rHS-DTX. In summary, rHS-DTX can provide a promising strategy for targeting therapy of metastatic breast cancer by improving the tumor-suppressing efficacy of DTX.
资助项目	National Basic Research Program of China[2014CB931900] ; National Natural Science Foundation of China[81630052] ; National Natural Science Foundation of China[81690265] ; National Natural Science Foundation of China[81521005] ; Key scientific research program of CAS[QYZDJ-SSW-SMC020] ; Youth Innovation Promotion Association of Chinese Academy of Sciences (CAS)[2015226]
WOS关键词	INFLAMMATORY MONOCYTES ; LUNG METASTASIS ; DRUG-RELEASE ; IN-VIVO ; NANOPARTICLES ; THERAPY
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:000430658300024
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279795]
专题	药物制剂研究中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Yin, Qi; Li, Yaping
作者单位	1.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Ctr Pharmaceut, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Lang, Tianqun,Ran, Wei,Dong, Xinyue,et al. Tumor Cells-Selective Bionic Nanodevice Exploiting Heparanase Combats Metastatic Breast Cancer[J]. ADVANCED FUNCTIONAL MATERIALS,2018,28(17).
APA	Lang, Tianqun.,Ran, Wei.,Dong, Xinyue.,Zheng, Zhong.,Liu, Yiran.,...&Li, Yaping.(2018).Tumor Cells-Selective Bionic Nanodevice Exploiting Heparanase Combats Metastatic Breast Cancer.ADVANCED FUNCTIONAL MATERIALS,28(17).
MLA	Lang, Tianqun,et al."Tumor Cells-Selective Bionic Nanodevice Exploiting Heparanase Combats Metastatic Breast Cancer".ADVANCED FUNCTIONAL MATERIALS 28.17(2018).