Targeting stem-property and vasculogenic mimicry for sensitizing paclitaxel therapy of triple-negative breast cancer by biomimetic codelivery.
10.1016/j.apsb.2025.04.006
- Author:
Siqi WU
1
;
Qing TANG
2
;
Weifeng FANG
3
;
Zhe SUN
1
;
Meng ZHANG
4
;
Ergang LIU
5
;
Yang CAO
1
;
Yongzhuo HUANG
1
Author Information
1. Department of Oncology, the First Affiliated Hospital and the First Clinical School of Guangzhou University of Chinese Medicine, Guangzhou 510000, China.
2. State Key Laboratory of Traditional Chinese Medicine Syndrome, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, Guangdong Provincial Hospital of Chinese Medicine, the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, China.
3. School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
4. Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
5. Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China.
- Publication Type:Journal Article
- Keywords:
Albumin;
Cancer stem-like cells;
Paclitaxel;
Pyruvate kinase M2 (PKM2);
Shikonin;
Triple-negative breast cancer;
Tumor microenvironment;
Vasculogenic mimicry
- From:
Acta Pharmaceutica Sinica B
2025;15(6):3226-3242
- CountryChina
- Language:English
-
Abstract:
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 co-encapsulate PTX and shikonin (SHK), a natural inhibitor of PKM2. By inhibiting PKM2, SHK suppressed β-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 epithelial-mesenchymal 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.
