The pursuit of innovative, multifunctional, more efficient, and safer treatments is a major challenge in preclinical nanoparticle-mediated thermotherapeutic research. Here, we report that iron oxide nanoparticles have the dual capacity to act as both magnetic and photothermal agents. We further explore every key aspect of this magnetophotothermal approach, choosing
iron oxide nanocubes for their high efficiency for the magnetic
hyperthermia modality itself. In aqueous
suspension, the nanocubes' exposure to both: an alternating magnetic field and near-infrared
laser irradiation (808 nm), defined as the DUAL-mode, amplifies the heating effect 2- to 5-fold by comparison with magnetic stimulation alone, yielding unprecedented heating powers (specific loss powers) up to 5000 W/g. In
cancer cells, the
laser excitation restores the optimal efficiency of magnetic
hyperthermia, otherwise inhibited by intracellular confinement, resulting in a remarkable heating efficiency in the DUAL-mode (up to 15-fold amplification), with respect to the magnetophotothermal mode. As a consequence, the dual action yielded complete apoptosis-mediated cell death. In solid
tumors in vivo, single-mode treatments (magnetic or
laser hyperthermia) reduced
tumor growth, while DUAL-mode treatment resulted in complete
tumor regression, mediated by heat-induced tumoral cell apoptosis and massive denaturation of the
collagen fibers, and a long-lasting thermal efficiency over repeated treatments.