Enhanced radiosensitization by liposome-encapsulated pimonidazole for anticancer effects on human melanoma cells.
The nitroimidazole-related hypoxic radiosensitizer, pimonidazole (Pmz) was encapsulated in liposome composed of dipalmitoylphosphatidylcholine, cholesterol and dipalmitoylphosphatidylglycerol (molar ratio = 1:1:0.2; diameter = 112.9 nm), and the radiosensitization was evaluated in human melanoma cells HMV-II. Cell proliferation was examined by WST-8 assay after X-ray irradiation in the presence of liposomal Pmz or free-Pmz under hypoxic conditions. On 7th day after X-ray irradiation of 5 Gy, cell proliferation decreased more markedly in the administration of liposomal Pmz than free-Pmz at equivalent Pmz doses. Chromatin fragmentation or nuclear condensation was observed in liposomal Pmz-treated HMV-II cells. Radiosensitization was enhanced dose-dependently along with Pmz amounts of 250-2000 microM contained in liposomal Pmz. Intracellular uptake was more abundant for liposomal Pmz for 60-240 min than for free-Pmz. Thus liposomal Pmz has a potential to overcome radiation resistance in hypoxia, owing to enhanced intracellular uptake by melanoma cells.
Radioisotope Centre, Osaka City University Graduate School of Medicine, Asahimachi 1-4-3, Abeno-ku, Osaka, 545-8585, Japan.
Shinya
S
Kato
Masatsugu
M
Kimura
Katsuhiro
K
Kageyama
Hiroshi
H
Tanaka
Nobuhiko
N
Miwa
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008422:Materials Testing; D008545:Melanoma / Q000473:pathology* / Q000503:physiopathology / Q000532:radiotherapy*; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D009593:Nitroimidazoles / Q000008:administration & dosage* / Q000737:chemistry; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry
D008081:Liposomes; D053769:Nanocapsules; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C033815:pimonidazole