N-propionyl-cysteaminylphenol-magnetite conjugate (NPrCAP/M) is a nanoparticle for the targeted growth suppression of melanoma cells.
A magnetite nanoparticle, NPrCAP/M, was produced for intracellular hyperthermia treatment of melanoma by conjugating N-propionyl-cysteaminylphenol (NPrCAP) with magnetite and used for the study of selective targeting and degradation of melanoma cells. NPrCAP/M, like NPrCAP, was integrated as a substrate in the oxidative reaction by mushroom tyrosinase. Melanoma, but not non-melanoma, cells incorporated larger amounts of iron than magnetite from NPrCAP/M. When mice bearing a B16F1 melanoma and a lymphoma on opposite flanks were given NPrCAP/M, iron was observed only in B16F1 melanoma cells and iron particles (NPrCAP/M) were identified within late-stage melanosomes by electron microscopy. When cells were treated with NPrCAP/M or magnetite and heated to 43 degrees C by an external alternating magnetic field (AMF), melanoma cells were degraded 1.7- to 5.4-fold more significantly by NPrCAP/M than by magnetite. Growth of transplanted B16 melanoma was suppressed effectively by NPrCAP/M-mediated hyperthermia, suggesting a clinical application of NPrCAP/M to lesional therapy for melanoma. Finally, melanoma cells treated with NPrCAP/M plus AMF showed little sub-G1 fraction and no caspase 3 activation, suggesting that the NPrCAP/M-mediated hyperthermia induced non-apoptotic cell death. These results suggest that NPrCAP/M may be useful in targeted therapy for melanoma by inducing non-apoptotic cell death after appropriate heating by the AMF.
Sato
Makito
M
Department of Dermatology, Sapporo Medical University, Sapporo, Japan.
Yamashita
Toshiharu
T
Ohkura
Masae
M
Osai
Yasue
Y
Sato
Akiko
A
Takada
Tomoaki
T
Matsusaka
Hidenobu
H
Ono
Ichiro
I
Tamura
Yasuaki
Y
Sato
Noriyuki
N
Sasaki
Yasushi
Y
Ito
Akira
A
Honda
Hiroyuki
H
Wakamatsu
Kazumasa
K
Ito
Shosuke
S
Jimbow
Kowichi
K
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D003538:Cystamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D052203:Ferrosoferric Oxide / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006979:Hyperthermia, Induced; D008280:Magnetics; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D014442:Monophenol Monooxygenase / Q000378:metabolism; D053758:Nanoparticles; D010636:Phenols / Q000378:metabolism / Q000494:pharmacology*
C114098:N-propionyl-4-S-cysteaminylphenol; D010636:Phenols; D014442:Monophenol Monooxygenase; D003538:Cystamine; D052203:Ferrosoferric Oxide