title: Growth inhibition of re-challenge B16 melanoma transplant by conjugates of melanogenesis substrate and magnetite nanoparticles as the basis for developing melanoma-targeted chemo-thermo-immunotherapy.
abstract: Melanogenesis substrate, N-propionyl-cysteaminylphenol (NPrCAP), is selectively incorporated into melanoma cells and inhibits their growth by producing cytotoxic free radicals. Magnetite nanoparticles also disintegrate cancer cells and generate heat shock protein (HSP) upon exposure to an alternating magnetic field (AMF). This study tested if a chemo-thermo-immunotherapy (CTI therapy) strategy can be developed for better management of melanoma by conjugating NPrCAP on the surface of magnetite nanoparticles (NPrCAP/M). We examined the feasibility of this approach in B16 mouse melanoma and evaluated the impact of exposure temperature, frequency, and interval on the inhibition of re-challenged melanoma growth. The therapeutic protocol against the primary transplanted tumor with or without AMF exposure once a day every other day for a total of three treatments not only inhibited the growth of the primary transplant but also prevented the growth of the secondary, re-challenge transplant. The heat-generated therapeutic effect was more significant at a temperature of 43 degrees C than either 41 degrees C or 46 degrees C. NPrCAP/M with AMF exposure, instead of control magnetite alone or without AMF exposure, resulted in the most significant growth inhibition of the re-challenge tumor and increased the life span of the mice. HSP70 production was greatest at 43 degrees C compared to that with 41 degrees C or 46 degrees C. CD8(+)T cells were infiltrated at the site of the re-challenge melanoma transplant.
authors.affiliation: Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Takada
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yamashita
authors.forename: Makito
authors.initials: M
authors.lastname: Sato
authors.forename: Akiko
authors.initials: A
authors.lastname: Sato
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ono
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyamoto
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Honda
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Wakamatsu
authors.forename: Shosuke
authors.initials: S
authors.lastname: Ito
authors.forename: Kowichi
authors.initials: K
authors.lastname: Jimbow
mesh_terms: D000818:Animals; D003538:Cystamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D052203:Ferrosoferric Oxide / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D006358:Hot Temperature; D007167:Immunotherapy; D008545:Melanoma / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000628:therapy*; D010636:Phenols / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D005609:Free Radicals; C114098:N-propionyl-4-S-cysteaminylphenol; D010636:Phenols; D003538:Cystamine; D052203:Ferrosoferric Oxide