Tumor Microenvironment-Responsive, Multistaged Liposome Induces Apoptosis and Ferroptosis by Amplifying Oxidative Stress for Enhanced Cancer Therapy

doi:10.1021/acsami.0c03564

科研成果详情

题名	Tumor Microenvironment-Responsive, Multistaged Liposome Induces Apoptosis and Ferroptosis by Amplifying Oxidative Stress for Enhanced Cancer Therapy
作者	Kou, Longfa1,2; Sun, Rui 1,2; Jiang, Xinyu 1,2,3; Lin, Xinlu 1,2; Huang, Huirong1,2; Bao, Shihui1,2; Zhang, Youting1,2; Li, Chao2,4; Chen, Ruijie1,2; Yao, Qing1,2,3
发表日期	2020-07-08
发表期刊	ACS APPLIED MATERIALS & INTERFACES 影响因子和分区
语种	英语
原始文献类型	Article
关键词	MMP2 response ATB(0,+) targeting liposomes xCT inhibition apoptosis ferroptosis
其他关键词	TRANSPORTER ATB(0,+) SLC6A14 ; MATRIX METALLOPROTEINASES ; GLUTAMINE-METABOLISM ; DRUG-DELIVERY ; UP-REGULATION ; RELEVANCE ; TARGETS
摘要	Tumor cells usually display metabolic, genetic, and microenvironment-related alterations, which are beneficial to tumor proliferation, tumor development, and resistance occurrence. Many transporters and enzymes, including ATB(0,+), xCT, and matrix metalloproteinases (MMPs), are involved in the altered cell metabolism and tumor microenvironment and often abnormally upregulated in malignant tumors. Meanwhile, these dysregulated transporters and enzymes provide targets not only for a pharmacological blockage to suppress tumor progress but also for tumor-specific delivery. Although transporters and MMPs have been widely reported for antitumor drug delivery, the feasibility of utilizing two strategies has never been elucidated yet. Herein, we developed an MMP2-activated and ATB(0,+)-targeted liposome with doxorubicin and sorafenib (DS@MA-LS) loaded for optimal tumor drug delivery for cancer therapy. DS@MA-LS was designed to prolong blood circulation and deshield the PEG shell from MMP2 cleavage to expose lysine and target overexpressed ATB(0,+) for enhanced tumor distribution and cancer cellular uptake. Besides the anticancer effects of loaded drugs, the endocytosed liposomes could further increase ROS production and suppress the antioxidant system to amplify oxidative stress. As expected, DS@MA-LS displayed enhanced targeted drug delivery to tumor sites with the MMP2-controlled ligand exposure and ATB(0,+)-mediated uptake. More importantly, DS@MA-LS successfully inhibited the tumor growth and cancer cell proliferation both in vitro and in vivo by enhancing apoptosis and ferroptosis, which thanks to the increased ROS generation and impaired GSH synthesis synergistically amplified oxidative stress. Our results suggested that the tumor microenvironment-responsive, multistaged nanoplatform, DS@MA-LS, has excellent potential for optimal drug delivery and enhanced cancer treatment.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81803443, 81903551]; Natural Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang Province [LQ19H300001]; Wenzhou Science and Technology Bureau [ZY2019007, Y20180180, Y20180208, Y20190177]
出版者	AMER CHEMICAL SOC
出版地	WASHINGTON
ISSN	1944-8244
EISSN	1944-8252
卷号	12 期号:27 页码:30031-30043
DOI	10.1021/acsami.0c03564
页数	13
WOS类目	Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS研究方向	Science & Technology - Other Topics ; Materials Science
WOS记录号	WOS:000550633400002
收录类别	SCIE ; PUBMED ; EI ; SCOPUS
EI入藏号	20203909215150
EI主题词	Targeted drug delivery
URL	查看原文
PubMed ID	32459093
SCOPUSEID	2-s2.0-85088207623
通讯作者地址	[Chen, Ruijie;Yao, Qing]Wenzhou Med Univ, Affiliated Hosp 2, Dept Pharm, Wenzhou 325035, Peoples R China.;Yao, Qing]Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325035, Peoples R China. ; [Yao, Qing]Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325027, Peoples R China.
Scopus学科分类	Materials Science (all)
TOP期刊	TOP期刊
引用统计	被引频次：25[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/1711
专题	附属第二医院药学院（分析测试中心）附属第二医院_科研中心第二临床医学院，附属第二医院、育英儿童医院
通讯作者	Chen, Ruijie; Yao, Qing
作者单位	1.Wenzhou Med Univ, Affiliated Hosp 2, Dept Pharm, Wenzhou 325035, Peoples R China; 2.Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325035, Peoples R China; 3.Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325027, Peoples R China; 4.Wenzhou Med Univ, Affiliated Hosp 2, Sci Ctr, Wenzhou 325027, Peoples R China
第一作者单位	附属第二医院; 第二临床医学院，附属第二医院、育英儿童医院
通讯作者单位	第二临床医学院，附属第二医院、育英儿童医院; 药学院（分析测试中心）
第一作者的第一单位	附属第二医院
推荐引用方式 GB/T 7714	Kou, Longfa,Sun, Rui,Jiang, Xinyu,et al. Tumor Microenvironment-Responsive, Multistaged Liposome Induces Apoptosis and Ferroptosis by Amplifying Oxidative Stress for Enhanced Cancer Therapy[J]. ACS APPLIED MATERIALS & INTERFACES,2020,12(27):30031-30043.
APA	Kou, Longfa., Sun, Rui., Jiang, Xinyu., Lin, Xinlu., Huang, Huirong., ... & Yao, Qing. (2020). Tumor Microenvironment-Responsive, Multistaged Liposome Induces Apoptosis and Ferroptosis by Amplifying Oxidative Stress for Enhanced Cancer Therapy. ACS APPLIED MATERIALS & INTERFACES, 12(27), 30031-30043.
MLA	Kou, Longfa,et al."Tumor Microenvironment-Responsive, Multistaged Liposome Induces Apoptosis and Ferroptosis by Amplifying Oxidative Stress for Enhanced Cancer Therapy".ACS APPLIED MATERIALS & INTERFACES 12.27(2020):30031-30043.