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Targeting stem-property and vasculogenic mimicry for sensitizing paclitaxel therapy of triple-negative breast cancer by biomimetic codelivery

文献类型：期刊论文

作者Wu, Siqi1,2,3; Tang, Qing4; Fang, Weifeng5; Sun, Zhe1,2; Zhang, Meng6; Liu, Ergang3; Cao, Yang1,2; Huang, Yongzhuo1,2,3,5,7
刊名ACTA PHARMACEUTICA SINICA B
出版日期2025-06-01
卷号15期号:6页码:3226-3242
关键词Shikonin Paclitaxel Triple-negative breast cancer Pyruvate kinase M2 (PKM2) Cancer stem-like cells Vasculogenic mimicry Tumor microenvironment Albumin
ISSN号2211-3835
DOI10.1016/j.apsb.2025.04.006
英文摘要Triple-negative breast cancer (TNBC) is aggressive, with high recurrence rates and poor prognosis. Paclitaxel (PTX) remains a key chemotherapeutic agent for TNBC, but its efficacy diminishes due to the emergence of drug resistance, largely driven by cancer stem-like cells (CSCs), vasculogenic mimicry (VM) formation and tumor immunosuppressive microenvironment (TIME). Pyruvate kinase M2 (PKM2) is highly expressed in TNBC, and is a potential target for TNBC treatment. In this study, we developed a biomimetic codelivery system using albumin nanoparticles (termed S/P NP) to coencapsulate PTX and shikonin (SHK), a natural inhibitor of PKM2. By inhibiting PKM2, SHK suppressed b-Catenin signaling, thereby reversing CSC stemness and preventing VM formation. The S/P NP system exhibited tumor-targeting delivery effect and significantly inhibited TNBC growth and lung metastasis. Mechanistically, the treatment reversed epithelialemesenchymal transition (EMT) and stem-like properties of TNBC cells, suppressed VM formation, and remodeled the TIME. It reduced immunosuppressive cells (M2 macrophages, MDSCs) while promoting anti-tumor immunity (M1 macrophages, dendritic cells, cytotoxic T cells, and memory T cells). This dual-action strategy holds promise for improving TNBC therapy by targeting CSCs, VM, and the immune microenvironment, and for overcoming PTX resistance and reducing metastasis. 2025 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
WOS关键词TUMOR ; CELLS ; METASTASIS ; PKM2 ; METABOLISM
资助项目National Key Research and Development Program of China[2024YFA1210200] ; National Key Research and Development Program of China[2022YFE0203600] ; NSFC (China)[82341232] ; NSFC (China)[82404549] ; NSFC (China)[82174456] ; Future Network (China)[083GJHZ2023012FN] ; Grand Challenges of the International Partnership Program of the Chinese Academy of Sciences (China)[083GJHZ2023021GC] ; CAS President's International Fellowship Initiative (China)[2024VBB0004] ; Department of Science and Technology of Guangdong Province (High-level Innovative Research Institute, China)[2021B0909050003] ; Zhongshan Municipal Bureau of Science and Technology (China)[LJ2021001] ; Zhongshan Municipal Bureau of Science and Technology (China)[CXTD202201] ; Second batch of social welfare and basic research projects of Zhongshan city (China)[2023B2033] ; Natural Science Foundation of Shanghai Municipal (China)[24ZR1477500]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001521723100004
出版者INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
源URL[http://119.78.100.183/handle/2S10ELR8/321057]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Cao, Yang; Huang, Yongzhuo
作者单位1.Guangzhou Univ Chinese Med, Affiliated Hosp 1, Dept Oncol, Guangzhou 510000, Peoples R China
2.Guangzhou Univ Chinese Med, Clin Sch 1, Guangzhou 510000, Peoples R China
3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
4.Guangzhou Univ Chinese Med, Guangdong Prov Hosp Chinese Med, State Key Lab Tradit Chinese Med Syndrome, Clin & Basic Res Team TCM Prevent & Treatment NSCL, Guangzhou 510000, Peoples R China
5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
6.Zhejiang Univ, Womens Hosp, Sch Med, Dept Pharm, Hangzhou 310006, Peoples R China
7.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		 Wu, Siqi,Tang, Qing,Fang, Weifeng,et al. Targeting stem-property and vasculogenic mimicry for sensitizing paclitaxel therapy of triple-negative breast cancer by biomimetic codelivery[J]. ACTA PHARMACEUTICA SINICA B,2025,15(6):3226-3242.
APA Wu, Siqi.,Tang, Qing.,Fang, Weifeng.,Sun, Zhe.,Zhang, Meng.,...&Huang, Yongzhuo.(2025).Targeting stem-property and vasculogenic mimicry for sensitizing paclitaxel therapy of triple-negative breast cancer by biomimetic codelivery.ACTA PHARMACEUTICA SINICA B,15(6),3226-3242.
MLA Wu, Siqi,et al."Targeting stem-property and vasculogenic mimicry for sensitizing paclitaxel therapy of triple-negative breast cancer by biomimetic codelivery".ACTA PHARMACEUTICA SINICA B 15.6(2025):3226-3242.

入库方式： OAI收割

来源：上海药物研究所

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