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Targeting lactate metabolism and immune interaction in breast tumor via protease-triggered delivery

文献类型：期刊论文

作者Zhao, Pengfei2; Wang, Shuang3,4; Jiang, Jizong5; Gao, Yanrong3,4; Wang, Yuewei3,4; Zhao, Yuge3; Zhang, Jiaxin3; Zhang, Meng6; Huang, Yongzhuo1,3,4,7,8
刊名JOURNAL OF CONTROLLED RELEASE
出版日期2023-06-01
卷号358页码:706-717
ISSN号0168-3659
关键词Legumain Lactate Tumor immune microenvironment (TIME) Quercetin Immunometabolism
DOI10.1016/j.jconrel.2023.05.024
通讯作者Jiang, Jizong(jiangjizong@shu.edu.cn) ; Huang, Yongzhuo(yzhuang@simm.ac.cn)
英文摘要Lactate is abundant in cancer tissues due to active glycolysis (aka Warburg effect) and mediates crosstalk between tumor cells and the immune microenvironment (TIME) to promote the progression of breast cancer. Quercetin (QU) is a potent monocarboxylate transporters (MCT) inhibitor, which can reduce lactate production and secretion of tumor cells. Doxorubicin (DOX) can induce immunogenic cell death (ICD), which promotes tumor-specific immune activation. Thus, we propose a combination therapy of QU & DOX to inhibit lactate metabolism and stimulate anti-tumor immunity. To enhance tumor-targeting efficiency, we developed a legumain-activatable liposome system (KC26-Lipo) with modification of KC26 peptide for co-delivery of QU & DOX for modulation of tumor metabolism and TIME in breast cancer. The KC26 peptide is a legumainresponsive, hairpin-structured cell-penetrating peptide (polyarginine) derivative. Legumain is a protease overexpressed in breast tumors, allowing selective activation of the KC26-Lipo to subsequently facilitate intratumoral and intracellular penetration. The KC26-Lipo effectively inhibited 4T1 breast cancer tumor growth through chemotherapy and anti-tumor immunity. Besides, inhibition of lactate metabolism suppressed the HIF1 & alpha;/VEGF pathway and angiogenesis and repolarized the tumor-associated macrophages (TAM). This work provides a promising breast cancer therapy strategy by regulating lactate metabolism and TIME.
WOS关键词IMMUNOGENIC CELL-DEATH ; LACTIC-ACID ; CANCER ; MACROPHAGES ; INHIBITION ; RESISTANCE ; QUERCETIN
资助项目National Key Research and Development Program of China[2021YFE0103100] ; National Key Research and Development Program of China[2021YFC2400600] ; NFSC[81925035] ; NFSC[81803736] ; NFSC[82204282] ; Chinese Pharmaceutical Association[CPAYLJ201901] ; Department of Science and Technology of Guangdong Province[2019B090904008] ; Department of Science and Technology of Guangdong Province[2021B0909050003] ; Zhongshan Municipal Bureau of Science and Technology[LJ2021001] ; Zhongshan Municipal Bureau of Science and Technology[CXTD2022011]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
出版者ELSEVIER
WOS记录号WOS:001012787600001
源URL[http://119.78.100.183/handle/2S10ELR8/306367]  
专题新药研究国家重点实验室
通讯作者Jiang, Jizong; Huang, Yongzhuo
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
2.Zhejiang Univ, Affiliated Hosp 2, Ctr Clin Pharmacol, Sch Med, 88 Jiefang Rd, Hangzhou 310009, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Shanghai Univ, Shanghai Engn Res Ctr Organ Repair, Sch Med, 99 Shangda Rd, Shanghai 200444, Peoples R China
6.Zhejiang Univ, Womens Hosp, Dept Pharm, Sch Med, 1 Xueshi Rd, Hangzhou 310006, Peoples R China
7.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Inst Drug Discovery & Dev, Zhongshan 528437, Peoples R China
8.NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipie, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Zhao, Pengfei,Wang, Shuang,Jiang, Jizong,et al. Targeting lactate metabolism and immune interaction in breast tumor via protease-triggered delivery[J]. JOURNAL OF CONTROLLED RELEASE,2023,358:706-717.
APA Zhao, Pengfei.,Wang, Shuang.,Jiang, Jizong.,Gao, Yanrong.,Wang, Yuewei.,...&Huang, Yongzhuo.(2023).Targeting lactate metabolism and immune interaction in breast tumor via protease-triggered delivery.JOURNAL OF CONTROLLED RELEASE,358,706-717.
MLA Zhao, Pengfei,et al."Targeting lactate metabolism and immune interaction in breast tumor via protease-triggered delivery".JOURNAL OF CONTROLLED RELEASE 358(2023):706-717.

入库方式： OAI收割

来源：上海药物研究所

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