Inhibition of breast cancer metastasis by dual liposomes to disturb complex formation

The interaction between tumour cells and blood components, mainly platelets, plays an important role in metastasis. In this study, the anti-metastatic effect of vesicles containing the cytotoxic drug perifosine (OPP) and the haemostatic inhibitor dipyridamole (DIP) was tested. These dual liposomes (DIP/OPP-L) encapsulating up to 400 μg DIP/ml and 6 mM OPP were prepared by extrusion technique. In vitro, DIP/OPP-L significantly inhibited the aggregation of platelets and reduced their adhesion to immobilized MT3 cells by up to 60% and 24.7%, respectively. Complex formation between platelets and tumour cells in vitro was completely prevented by DIP/OPP-vesicles. These combinatory liposomes also inhibited the metastatic capacity of circulating tumour cells by reducing the complex formation with platelets. Formation of lung and extrapulmonary metastases after intravenous administration of MT3 breast cancer cells was significantly reduced when mice were treated with a single intravenous dose of DIP/OPP-L containing 100 nmol lipid 6 h before tumour cell inoculation.