A selenium- containing selective histone deacetylase 6 inhibitor for targeted in vivo breast tumor imaging and therapy

doi:10.1039/c9tb00383e

CORC > 自动化研究所 > 中国科学院自动化研究所 > 中国科学院分子影像重点实验室

	A selenium- containing selective histone deacetylase 6 inhibitor for targeted in vivo breast tumor imaging and therapy
	Tang, Chu 1,2; Du, Yang2,3,4 ; Liang, Qian 2; Cheng, Zhen 5,6; Tian, Jie1,2,3,4
刊名	JOURNAL OF MATERIALS CHEMISTRY B
	2019-06-14
卷号	7 期号:22 页码:3528-3536
ISSN号	2050-750X
DOI	10.1039/c9tb00383e
通讯作者	Cheng, Zhen(zcheng@stanford.edu) ; Tian, Jie(jie.tian@ia.ac.cn)
英文摘要	Early detection and effective treatment are essential for the management of breast cancer, especially for triple-negative breast cancer (TNBC). However, current imaging methods and treatment strategies are ineffective because of the lack of efficient biomarkers and molecular targets. Thus, identifying novel biomarkers and their corresponding ligands is critical for controlling breast cancer. Histone deacetylase 6 (HDAC6) has emerged as a valid target for cancer therapy owing to its selective tumor inhibition and fewer side effects compared to pan-HDAC- and HDAC1-3 isoform-selective inhibitors. Here, a HDAC6-selective inhibitor, SelSA, was developed by utilizing a selenocyanide moiety instead of the conventional hydroxamic acid core, which showed 112-fold and 128-fold selective binding affinity for HDAC6 relative to HDAC1 and HDAC8. In vitro studies demonstrated that FITC-SelSA was specifically uptaken by both ER alpha(+) MCF-7 and TNBC MDA-MB-231 cells, with primarily cytoplasmic localization. SelSA reactivated ER alpha expression and sensitized TNBC cell responses to the antagonist tamoxifen, and displayed potent antitumor effects against both MCF-7 and MDA-MB-231 cells in vitro and tumor xenografts in vivo with no obvious side effects. Moreover, in in vivo near-infrared fluorescence imaging to assess SelSA biodistribution, the IRDye800CW-SelSA probe exhibited specific tumor targeting ability with high tumor-to-normal tissue contrast. The in vivo tumor treatment study revealed that SelSA possessed improved treatment efficacy and fewer side effects in both ER alpha(+) and TNBC tumors, compared to pan-HDAC inhibitors. Overall, our study indicated that the HDAC6 inhibitor SelSA is a highly promising candidate for targeted breast cancer imaging and therapy with clinical translational potential.
资助项目	National Key Research and Development Program of China[2017YFA0205200] ; National Key Research and Development Program of China[2016YFA0201401] ; National Key Research and Development Program of China[2016YFC0103702] ; National Key Research and Development Program of China[2016YFC0102000] ; National Natural Science Foundation of China[81227901] ; National Natural Science Foundation of China[81470083] ; National Natural Science Foundation of China[81527805] ; National Natural Science Foundation of China[61231004] ; National Natural Science Foundation of China[81601548] ; National Natural Science Foundation of China[81772011] ; International Innovation Team of CAS[20140491524] ; Beijing Municipal Science & Technology Commission[Z161100002616022] ; China Postdoctoral Science Foundation[2017M613084] ; Shaanxi Postdoctoral Science Foundation[2017BSHEDZZ91]
WOS关键词	ESTROGEN-RECEPTOR ; HDAC6 INHIBITOR ; CANCER ; DESIGN ; TRICHOSTATIN ; FLUORESCENT ; GROWTH
WOS研究方向	Materials Science
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000472230200004
资助机构	National Key Research and Development Program of China ; National Natural Science Foundation of China ; International Innovation Team of CAS ; Beijing Municipal Science & Technology Commission ; China Postdoctoral Science Foundation ; Shaanxi Postdoctoral Science Foundation
内容类型	期刊论文
源URL	[http://ir.ia.ac.cn/handle/173211/26062]
专题	自动化研究所_中国科学院分子影像重点实验室
通讯作者	Cheng, Zhen; Tian, Jie
作者单位	1.Xidian Univ, Sch Life Sci & Technol, Minist Educ, Engn Res Ctr Mol & Neuro Imaging, Xian 710126, Shaanxi, Peoples R China 2.Chinese Acad Sci, CAS Key Lab Mol Imaging, State Key Lab Management & Control Complex Syst, Inst Automat, Beijing 100190, Peoples R China 3.Beijing Key Lab Mol Imaging, Beijing 100190, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100080, Peoples R China 5.Stanford Univ, Dept Radiol, MIPS, Stanford, CA 94305 USA 6.Stanford Univ, BioX Program, Canary Ctr, Stanford Canc Early Detect, Stanford, CA 94305 USA
推荐引用方式 GB/T 7714	Tang, Chu,Du, Yang,Liang, Qian,et al. A selenium- containing selective histone deacetylase 6 inhibitor for targeted in vivo breast tumor imaging and therapy[J]. JOURNAL OF MATERIALS CHEMISTRY B,2019,7(22):3528-3536.
APA	Tang, Chu,Du, Yang,Liang, Qian,Cheng, Zhen,&Tian, Jie.(2019).A selenium- containing selective histone deacetylase 6 inhibitor for targeted in vivo breast tumor imaging and therapy.JOURNAL OF MATERIALS CHEMISTRY B,7(22),3528-3536.
MLA	Tang, Chu,et al."A selenium- containing selective histone deacetylase 6 inhibitor for targeted in vivo breast tumor imaging and therapy".JOURNAL OF MATERIALS CHEMISTRY B 7.22(2019):3528-3536.