Enhanced Cytotoxicity of Doxorubicin by Micellar Photosensitizer-mediated Photochemical Internalization in Drug-resistant MCF-7 Cells

Abstract

Multiple drug resistance (MDR) is a major clinical problem that seriously reduces the efficacy of many chemotherapy agents. In doxorubicin-resistant breast cancer cells, drugs accumulate only within discrete cytoplasmic organelles and almost none is detectable in the nuclei, the target of anthracycline drugs. Photochemical internalization (PCI), a specific branch of photodynamic therapy, is a novel technology utilized for the site-specific release of macromolecules within cells. In this study, the phototoxicity of dendrimer phthalocyanine (DPc)-encapsulated polymeric micelle (DPc/m) combined with doxorubicin was studied in drug-resistant MCF-7 cells. After photoirradiation with a LED (670 nm), the internalized DPc/m showed unique photochemical processes inside of the cells that can disrupt the endosomal/lysosomal membrane and thereby cause the doxorubicin release from the lysosome to nuclei. In conclusion, DPc/m-mediated PCI destroyed endosomal/ lysosomal membrane efficiently that can reverse the MDR phenotype of doxorubicin resistant MCF-7 cells. The technique is a promising new approach to overcome the drugresistance in breast cancer cells.