Multidrug resistance bypass in cells exposed to doxorubicin-loaded nanospheres. Absence of endocytosis.
Multidrug resistance bypass has been achieved in vitro with polyalkylcyanoacrylate nanospheres loaded with doxorubicin as previously shown by Cuvier et al. Fluorescence-imaging experiments were performed to determine if the endocytosis of the particles by the cells could be responsible for this activity. The results obtained with three lines of sensitive and resistant cells (K562, MCF7, and C6) demonstrate that the particles were not internalized by the cells, nor were they adsorbed onto the cell surface. In contrast, these nanospheres were very efficiently endocytosed by phagocytic cells such as macrophages. No correlation was observed between the fate of the particles, endocytosed or not, and their cytotoxic activity. It was concluded that no endocytosis step was involved in the mechanism of the multidrug resistance bypass obtained by associating a drug to polymeric particles.
D000818:Animals; D002478:Cells, Cultured; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers; D018432:Drug Resistance, Multiple; D004705:Endocytosis; D006801:Humans; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D008863:Microspheres; D051381:Rats; D014407:Tumor Cells, Cultured
D004337:Drug Carriers; D004317:Doxorubicin