https://doi.org/10.1016/j.apsb.2025.04.006
This new article publication from Acta Pharmaceutica Sinica B , discusses targeting stem-property and vasculogenic mimicry for sensitizing paclitaxel therapy of triple-negative breast cancer by biomimetic codelivery.
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.
The authors of this article 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.
Keywords: Shikonin, Paclitaxel, Triple-negative breast cancer, Pyruvate kinase M2 (PKM2), Cancer stem-like cells, Vasculogenic mimicry, Tumor microenvironment, Albumin
Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S2211383525002382-ga1_lrg.jpg
A combination therapeutic strategy using the albumin co-loading shikonin (SHK) and paclitaxel (PTX) was developed for TNBC treatment, which can inhibit PKM2 and β -Catenin, leading to suppression stem-property and vasculogenic mimicry.
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The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association .
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CiteScore: 24.3
Impact Factor: 14.6 (Top 6 journal in the category of Pharmacology and pharmacy)
JIF without self-citation: 13.8
ISSN 2211-3835
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Siqi Wu, Qing Tang, Weifeng Fang, Zhe Sun, Meng Zhang, Ergang Liu, Yang Cao, Yongzhuo Huang, Targeting stem-property and vasculogenic mimicry for sensitizing paclitaxel therapy of triple-negative breast cancer by biomimetic codelivery, Acta Pharmaceutica Sinica B, Volume 15, Issue 6, 2025,
Pages 3226-3242, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2025.04.006
Acta Pharmaceutica Sinica B