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Glutathione-Disrupting Nanotherapeutics Potentiate Ferroptosis for Treating Luminal Androgen Receptor-Positive Triple-Negative Breast Cancer

文献类型：期刊论文

作者Li, Jie4,5; Wu, Yao2,3; Li, Yongping1; Zhu, Hongbo1; Zhang, Zhiwen2,3; Li, Yaping4,5
刊名ACS NANO
出版日期2024-09-17
卷号18期号:39页码:26585-26599
关键词glutathione glutathioneperoxidase 4 ferroptosis nanotherapeutics triple-negative breast cancer
ISSN号1936-0851
DOI10.1021/acsnano.4c04322
通讯作者Zhang, Zhiwen(zhangzhiwen@fudan.edu.cn) ; Li, Yaping(ypli@simm.ac.cn)
英文摘要The refractory luminal androgen receptor (LAR) subtype of triple-negative breast cancer (TNBC) patients is challenged by significant resistance to neoadjuvant chemotherapy and increased immunosuppression. Regarding the distinct upregulation of glutathione (GSH) and glutathione peroxidase 4 (GPX4) in LAR TNBC tumors, we herein designed a GSH-depleting phospholipid derivative (BPP) and propose a BPP-based nanotherapeutics of RSL-3 (GDNS), aiming to deplete intracellular GSH and repress GPX4 activity, thereby potentiating ferroptosis for treating LAR-subtype TNBC. GDNS treatment drastically downregulated the expression of GSH and GPX4, resulting in a 33.88-fold enhancement of lipid peroxidation and significant relief of immunosuppression in the 4T1 TNBC model. Moreover, GDNS and its combination with antibody against programed cell death protein 1 (antiPD-1) retarded tumor growth and produced 2.83-fold prolongation of survival in the LAR-positive TNBC model. Therefore, the GSH-disrupting GDNS represents an encouraging strategy to potentiate ferroptosis for treating refractory LAR-subtype TNBC.
WOS关键词CELL-DEATH ; PH
资助项目National Key R&D Program of China[2022YFC3401400] ; National Key R&D Program of China[2022YFC2304303] ; National Key R&D Program of China[2023YFE0104300] ; National Natural Science Foundation of China[32271461] ; Science and Technology Development Fund of Shanghai Pudong New Area[PKJ2019-Y28]
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science
语种英语
WOS记录号WOS:001314988000001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/313439]  
专题新药研究国家重点实验室
通讯作者Zhang, Zhiwen; Li, Yaping
作者单位1.Fudan Univ, Shanghai Pudong Hosp, Pudong Med Ctr, Dept Breast Surg, Shanghai, Peoples R China
2.Fudan Univ, Minist Educ, Key Lab Smart Drug Delivery, Shanghai 201203, Peoples R China
3.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Li, Jie,Wu, Yao,Li, Yongping,et al. Glutathione-Disrupting Nanotherapeutics Potentiate Ferroptosis for Treating Luminal Androgen Receptor-Positive Triple-Negative Breast Cancer[J]. ACS NANO,2024,18(39):26585-26599.
APA Li, Jie,Wu, Yao,Li, Yongping,Zhu, Hongbo,Zhang, Zhiwen,&Li, Yaping.(2024).Glutathione-Disrupting Nanotherapeutics Potentiate Ferroptosis for Treating Luminal Androgen Receptor-Positive Triple-Negative Breast Cancer.ACS NANO,18(39),26585-26599.
MLA Li, Jie,et al."Glutathione-Disrupting Nanotherapeutics Potentiate Ferroptosis for Treating Luminal Androgen Receptor-Positive Triple-Negative Breast Cancer".ACS NANO 18.39(2024):26585-26599.

入库方式： OAI收割

来源：上海药物研究所

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