期刊
JOURNAL OF DRUG TARGETING
卷 23, 期 4, 页码 335-346出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/1061186X.2014.996760
关键词
B16F10 melanoma; liposome; low-molecular-weight heparin; lung metastasis; P-selectin
资金
- Program for New Century Excellent Talents [NCET-11-0736]
- Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University [JKGP201102]
Tumor metastasis is the biggest challenge in cancer therapy. During the metastasis process, metastatic cells could acquire stealth ability toward immune system through the formation of a protection cloak by hijacking platelets (PTs). Heparins, a heterogeneous mixture of glycosaminoglycans, can inhibit metastatic cascades by blocking P-selectin-mediated intercellular adhesion between tumor cells and PTs. In this study, low-molecular-weight heparin-coated doxorubicin-loaded liposome (LMWH-DOX-Lip) was developed for metastasis preventative therapy. The formation of LMWH-DOX-Lip was based on electrostatic interactions between the negatively charged heparins and cationic lipids. LMWH-DOX-Lip prepared at the optimum prescription possessed high entrapment efficiency, ideal particle size and zeta potential. Morphology of LMWH-DOX-Lip was characterized by atomic force microscopy and transmission electron microscopy. The results of confocal microscopic observations and flow cytometry analysis indicated that LMWH-DOX-Lip mediated an efficient cellular uptake in B16F10 melanoma cell line. Besides, LMWH-DOX-Lip displayed an increased cytotoxic over their unmodified counterparts. Furthermore, the inhibition effect of LMWH-DOX-Lip on adhesion between tumor cells and PTs/P-selectin was observed. In vivo study performed on a pulmonary melanoma mouse model revealed a substantially tumor metastasis prevention by LMWH-DOX-Lip. All these results suggested that LMWH-DOX-Lip could significantly inhibit metastasis through preventing the tumor cell-platelet interactions and in the meantime suppressed tumor growth.
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