Melanogenesis Exploitation and Melanoma Nanomedecine: Utilization of Melanogenesis Substrate, NPrCAP for Exploiting Melanoma-Targeting Drug and its Conjugation with Magnetite Nanoparticles for Developing Melanoma Chemo-Thermo-Immunotherapy

Exploitation of a specific biological property is one of the best approaches for developing novel cancer-targeted drugs. Melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP: amine analog of tyrosine) may provide a unique drug delivery system (DDS) because of its selective incorporation into melanoma cells. It may also act as a melanoma-targeted therapeutic drug because of its production of highly reactive free radicals (melanoma-targeted chemotherapy). Utilization of magnetite nanoparticles can also be a good platform to develop thermo-immunotherapy because of heat shock protein (HSP) generation upon exposure to the alternating magnetic field (AMF). This study shows the feasibility of this approach in experimental study using in vivo and in vitro B16 melanoma cells and preliminary clinical study to a limited number of advanced melanoma patients. The therapeutic protocol against the primarily transplanted tumor with or without AMF once a day every other day for a total of three treatments not only inhibited the growth of primary transplant, but also prevented the growth of the secondary, re-challenge transplant and increased life span of the host mice. HSP70 production at the site of primary transplant and CD8 + T cell infiltration at the site of the re- challenge melanoma transplant were seen. Four patients entered in the preliminary clinical trial by following the basic outline of this animal protocol and two of them showed PR and CR. We hope to establish in situ vaccination immunotherapy for melanoma metastases by melanogenesis-targeted chemo- and thermotherapy.