Loaded CA4P and rapamycin acid-sensitive liposomes target blood vessels for the treatment of triple-negative breast cancer
10.16438/j.0513-4870.2024-0207
- VernacularTitle:负载CA4P和雷帕霉素酸敏感脂质体靶向血管治疗三阴性乳腺癌
- Author:
Dong-jie ZHU
;
Meng TIAN
;
Yuan-yan LIU
- Publication Type:Research Article
- Keywords:
combretastatin A4 phosphate disodium;
rapamycin;
pH-sensitive nanocarrier;
vascular disrupting strategy;
triple negative breast cancer
- From:
Acta Pharmaceutica Sinica
2024;59(7):2143-2152
- CountryChina
- Language:Chinese
-
Abstract:
Given the vital role of vasculature in solid tumors, the potential of vascular disrupting therapy in the treatment of triple-negative breast cancer (TNBC) is promising. In this study, we prepared the acid-sensitive liposome PPD/CA4P/Lip-Rap loaded with the vascular disrupting agent CA4P and the anti-angiogenic drug rapamycin (Rap) to explore the potential of the vascular disrupting strategy in TNBC. PPD/CA4P/Lip-Rap was characterized by 1H NMR, dynamic light scattering, and transmission electron microscopy. Its drug loading and acid sensitivity were determined. The particle size of PPD/CA4P/Lip-Rap is 161.53 ± 1.89 nm, the zeta potential is -20.03 ± 0.9 mV and it demonstrated good drug release on acidic sensitivity responses. CCK-8 experiments proved that Rap can enhance the ability of CA4P to destroy tumor vascular endothelial cells. Rap can kill marginal residual tumor cells, suppress tumor recurrence. Nanocarriers can further enhance the therapeutic effect. Western blot (WB) showed that Rap decreased the expression of hypoxia-inducible factor-1α (HIF-1α) via the mTOR/p70S6K and mTOR/4E-BP1 pathways. Thus, tumor hypoxia activation and angiogenesis were inhibited. PPD/CA4P/Lip-Rap can effectively destroy tumor vessels, inhibit tumor angiogenesis and recurrence, and provide a new strategy for the treatment of TNBC by targeting disruption of tumor vessels.
