An exosome-like programmable-bioactivating paclitaxel prodrug nanoplatform for enhanced breast cancer metastasis inhibition

doi:10.1016/j.biomaterials.2020.120224

	An exosome-like programmable-bioactivating paclitaxel prodrug nanoplatform for enhanced breast cancer metastasis inhibition
	Wang, Kaiyuan 1; Ye, Hao 1; Zhang, Xuanbo 1; Wang, Xia 2; Yang, Bin 3,4; Luo, Cong 1; Zhao, Zhiqiang 1; Zhao, Jian 2; Lu, Qi 1; Zhang, Haotian 5
刊名	BIOMATERIALS
	2020-10-01
卷号	257 页码:13
关键词	Exosome membrane Cucurbitacin B Paclitaxel Breast cancer metastasis Programmable bioactivation
ISSN号	0142-9612
DOI	10.1016/j.biomaterials.2020.120224
通讯作者	Sun, Jin(sunjin@syphu.edu.cn)
英文摘要	Metastasis is closely associated with high breast cancer mortality. Although nanotechnology-based anti-metastatic treatments have developed rapidly, the anti-metastasis efficiency is still far from satisfactory, mainly due to the poor recognition of circulating tumor cells (CTCs) in blood. Herein, we developed an exosome-like sequential-bioactivating prodrug nanoplatform (EMPCs) to overcome the obstacle. Specifically, the reactive oxygen species (ROS)-responsive thioether-linked paclitaxel-linoleic acid conjugates (PTX-S-LA) and cucurbitacin B (CuB) are co-encapsulated into polymeric micelles, and the nanoparticles are further decorated with exosome membrane (EM). The resulting EMPCs could specifically capture and neutralize CTCs during blood circulation through the high-affinity interaction between cancer cell membrane and homotypic EM. Following cellular uptake, EMPCs first release CuB, remarkably blocking tumor metastasis via downregulation of the FAK/MMP signaling pathway. Moreover, CuB obviously elevates the intracellular oxidative level to induce a sequential bioactivation of ROS-responsive PTX-S-LA. In vitro and in vivo results demonstrate that EMPCs not only exhibit amplified prodrug bioactivation, prolonged blood circulation, selective targeting of homotypic tumor cells, and enhanced tumor penetration, but also suppress tumor metastasis through CTCs clearance and FAK/MMP signaling pathway regulation. This study proposes an integrated approach for mechanism-based inhibition of tumor metastasis and manifests a promising potential of programmable-bioactivating prodrug nanoplatform for cancer metastasis inhibition.
资助项目	National Natural Science Foundation of China[81773656] ; National Natural Science Foundation of China[U1608283] ; Liaoning Revitalization Talents Program[XLYC1808017] ; Key projects of Technology Bureau in Shenyang[18400408] ; Key projects of Liaoning Province Department of Education[2017LZD03]
WOS关键词	CUCURBITACIN B ; NANOPARTICLES ; CELLS ; ROS
WOS研究方向	Engineering ; Materials Science
语种	英语
出版者	ELSEVIER SCI LTD
WOS记录号	WOS:000563938200002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/292366]
专题	中国科学院上海药物研究所
通讯作者	Sun, Jin
作者单位	1.Shenyang Pharmaceut Univ, Wuya Coll Innovat, Dept Pharmaceut, Shenyang 110016, Liaoning, Peoples R China 2.Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, Liaoning, Peoples R China 3.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Ctr Pharmaceut, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 5.Shenyang Pharmaceut Univ, Sch Life Sci & Biopharmaceut, Shenyang 110016, Liaoning, Peoples R China
推荐引用方式 GB/T 7714	Wang, Kaiyuan,Ye, Hao,Zhang, Xuanbo,et al. An exosome-like programmable-bioactivating paclitaxel prodrug nanoplatform for enhanced breast cancer metastasis inhibition[J]. BIOMATERIALS,2020,257:13.
APA	Wang, Kaiyuan.,Ye, Hao.,Zhang, Xuanbo.,Wang, Xia.,Yang, Bin.,...&Sun, Jin.(2020).An exosome-like programmable-bioactivating paclitaxel prodrug nanoplatform for enhanced breast cancer metastasis inhibition.BIOMATERIALS,257,13.
MLA	Wang, Kaiyuan,et al."An exosome-like programmable-bioactivating paclitaxel prodrug nanoplatform for enhanced breast cancer metastasis inhibition".BIOMATERIALS 257(2020):13.