Tyrosine analogs are good candidates for developing
melanoma chemotherapies because melanogenesis is inherently toxic and expressed uniquely in melanocytic cells. The
sulfur homolog of
tyrosine,
4-S-cysteaminylphenol (4-S-CAP), was shown to be a substrate of
melanoma tyrosinase and can cause selective cytotoxicity of melanocytes and
melanoma cells. Previously, in order to improve the adsorption of magnetite nanoparticles to target cell surfaces, and generate heat in an alternating magnetic field (AMF) for
cancer hyperthermia, we produced
hyperthermia using
magnetite cationic
liposomes (MCL) that have a positive charge at the liposomal surface. In the present study, we constructed 4-S-CAP-loaded MCL (4-S-CAP/MCL), which act as a novel modality, combining
melanoma-specific
chemotherapy by 4-S-CAP with intracellular
hyperthermia mediated by MCL. The 4-S-CAP/MCL exerted 4-S-CAP-mediated anticancer effects on
B16 melanoma cells in vitro and in vivo. Moreover, after intratumoral injection of 4-S-CAP/MCL in vivo, the
melanoma nodules were heated to 45 degrees C under an AMF. Significantly higher
therapeutic effects were observed in mice treated with the combination
therapy mediated by 4-S-CAP/MCL plus AMF irradiation compared with mice treated with 4-S-CAP/MCL alone (without AMF) or mice treated with
hyperthermia alone (MCL + AMF irradiation). These results suggest that this novel therapeutic tool is applicable to the treatment of
malignant melanoma.