PH and NIR-light-responsive magnetic iron oxide nanoparticles for mitochondria-mediated apoptotic cell death induced by chemo-photothermal therapy

Abstract

Recently, various therapeutic strategies in anticancer drug development are focused to reduce adverse side effects and to enhance the therapeutic efficacy. Mostly, the iron oxide (Fe3O4) nanoparticles have widely been utilized as an efficient drug delivery system towing to their unique properties such as excellent magnetic behavior, considerably low toxicity, easy surface modification and high drug-loading efficacy. In the present study, we synthesized a multifunctional, DMSA coated, water soluble Fe3O4 nanoparticles (Fe3O4@DMSA/DOX) for an effective pH and NIR-light triggered delivery of anticancer drug (DOX) in cancer therapy. The combination of photothermal therapy combined with chemotherapy results demonstrated that the synthesized Fe3O4@DMSA/DOX is an excellent candidate for pH- and NIR-light induced phothothermal agent for an effective delivery of anticancer drug (DOX) into the target sub-cellular level into the human breast cancer (MDA-MB-231) cells. Furthermore, the Fe3O4@DMSA/DOX nanoparticles induced an excellent temperature elevation upon NIR light irradiation and controlled DOX release in vitro. The Fe3O4@DMSA/DOX nanoparticles exhibited synergistic effect when combining chemotherapy with photothermal therapy and showed an excellent cell toxicity to MDA-MB-231 cells. In addition, the combined chemo-photothermal therapy of Fe3O4@DMSA/DOX nanoparticles promoted an effective cell death by mitochondrial disruption mediated by ROS generation. Thus, the synthesized Fe3O4@DMSA/DOX nanoparticles could be utilized as potential anticancer agents for breast cancer treatment.