Iontophoresis alters liposome internalization and lysosome expression in tumor cells

Iontophoresis is a physical method that uses a constant electric current to increase the permeation of drugs through the skin. Associated with liposomes, it targets the release of encapsulated drugs to specific layers of the skin1. The objective of this study was to investigate the influence of iontophoresis on the internalization pathways and intracellular traffic of liposomes. Previously characterized 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO)-labeled liposomes, 200 nm, had their internalization pathways investigated in A431 skin carcinoma cells by inhibiting macropinocytosis, caveolin, clathrin and clathrin and caveolin independent routes using, respectively 5-(N-ethyl-N-isopropyl) amyloride (EIPA), genistein, chlorpromazine and dinasore. LAMP1 was used for lysosome labeling. In the absence of iontophoresis, liposomes were internalized by non-endocytic pathways. The application of 10 min of iontophoresis resulted in macropinocytosis and caveolin mediated liposome internalization. In addition, lysosome expression was significantly reduced by liposome iontophoresis. Therefore, iontophoresis alters nanoparticle cell internalization pathways and the expression pattern of lysosomes.