MULTIDRUG-RESISTANCE BYPASS IN CELLS EXPOSED TO DOXORUBICIN-LOADED NANOSPHERES - ABSENCE OF ENDOCYTOSIS

Multidrug resistance bypass has been achieved in vitro with polyalkylc yanoacrylate nanospheres loaded with doxorubicin as previously shown b y Cuvier et al. Fluorescence-imaging experiments were performed to det ermine if the endocytosis of the particles by the cells could be respo nsible for this activity. The results obtained with three lines of sen sitive and resistant cells (K562, MCF7, and C6) demonstrate that the p articles were not internalized by the cells, nor were they adsorbed on to the cell surface. In contrast, these nanospheres were very efficien tly endocytosed by phagocytic cells such as macrophages. No correlatio n was observed between the fate of the particles, endocytosed or not, and their cytotoxic activity. It was concluded that no endocytosis ste p was involved in the mechanism of the multidrug resistance bypass obt ained by associating a drug to polymeric particles.