title: Lysosomal membrane permeabilization by targeted magnetic nanoparticles in alternating magnetic fields.
abstract: Lysosomal death pathways are being explored as alternatives of overcoming cancer tumor resistance to traditional forms of treatment. Nanotechnologies that can selectively target and induce permeabilization of lysosomal compartments in cells could become powerful medical tools. Here we demonstrate that iron oxide magnetic nanoparticles (MNPs) targeted to the epidermal growth factor receptor (EGFR) can selectively induce lysosomal membrane permeabilization (LMP) in cancer cells overexpressing the EGFR under the action of an alternating magnetic field (AMF). LMP was observed to correlate with the production of reactive oxygen species (ROS) and a decrease in tumor cell viability. Confocal microscopy images showed an increase in the cytosolic activity of the lysosomal protease cathepsin B. These observations suggest the possibility of remotely triggering lysosomal death pathways in cancer cells through the administration of MNPs which target lysosomal internalization pathways and the application of AMFs.
authors.affiliation: Department of Chemical Engineering, University of Puerto Rico, Mayaguez, Puerto Rico 00681.
authors.forename: Maribella
authors.initials: M
authors.lastname: Domenech
authors.forename: Ileana
authors.initials: I
authors.lastname: Marrero-Berrios
authors.forename: Madeline
authors.initials: M
authors.lastname: Torres-Lugo
authors.forename: Carlos
authors.initials: C
authors.lastname: Rinaldi
mesh_terms: D001692:Biological Transport; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism; D005290:Ferric Compounds / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D060526:Magnetic Fields; D053758:Nanoparticles; D010539:Permeability
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide; C512478:EGFR protein, human; D066246:ErbB Receptors