title: Enhanced radiosensitization by the cationic liposome-encapsulated thymidine analogue BrdU through the increased intracellular BrdU-uptake on human melanoma as compared to anionic or nonionic liposomal or free BrdU.
abstract: The synthetic thymidine analogue, 5-bromo-2'-deoxy-uridine (BrdU) was encapsulated in cationic liposome composed of dipalmitoylphosphatidylcholine, cholesterol and stearylamine (molar ratio = 1/1/0.2; diameter = 120 nm), and the radiosensitization of cationic liposomal BrdU was assessed on human melanoma cells HMV-II, with comparing to anionic or nonionic liposomal BrdU and free-BrdU. HMV-II cells were pretreated by cationic liposomal BrdU or free-BrdU and then exposed to X-ray, followed by WST-8 assay to examine cell proliferation. The radiation-induced change of nuclei was defined with Hoechst33342 staining. The rates of thymidine replacement by BrdU and DNA double-strand breaks on HMV-II cells were determined with an anti-BrdU antibody and anti-53BP1 antibody, respectively. On 7th day after X-ray irradiation at 3 Gy, cell proliferation was suppressed more markedly in the administration of cationic liposomal BrdU than free-BrdU at equivalent BrdU doses. Giant polykaryocytes were observed in cationic liposomal BrdU-treated HMV-II cells. Radiosensitization was enhanced dose-dependently along with BrdU doses of 0.1-0.8 μM in the order: cationic liposomal BrdU > anionic liposomal BrdU > nonionic liposomal BrdU (see symbol) free-BrdU. Similarly, the cationic liposomal BrdU augmented the rate of thymidine-moiety replacement by BrdU and DNA double-strand breaks more appreciably than free-BrdU. Therefore, the cationic liposome-encapsulation of BrdU would be one of favorable drug deliveries for facilitating the X-ray therapy against cancer.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kato
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Kimura
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Miwa
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D001973:Bromodeoxyuridine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D002412:Cations; D045744:Cell Line, Tumor; D004058:Diffusion; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008657:Metabolic Clearance Rate; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D002412:Cations; D008081:Liposomes; D053769:Nanocapsules; D011838:Radiation-Sensitizing Agents; D001973:Bromodeoxyuridine