title: NK105, a paclitaxel-incorporating micellar nanoparticle, is a more potent radiosensitising agent compared to free paclitaxel.
abstract: NK105 is a micellar nanoparticle formulation designed to enhance the delivery of paclitaxel (PTX) to solid tumours. It has been reported to exert antitumour activity in vivo and to have reduced neurotoxicity as compared to that of free PTX. The purpose of this study was to investigate the radiosensitising effect of NK105 in comparison with that of PTX. Lewis lung carcinoma (LLC)-bearing mice were administered a single intravenous (i.v.) injection of PTX or NK105; 24 h after the drug administration, a proportion of the mice received radiation to the tumour site or lung fields. Then, the antitumour activity and lung toxicity were evaluated. In one subset of mice, the tumours were excised and specimens were prepared for analysis of the cell cycle distribution by flow cytometry. Combined NK105 treatment with radiation yielded significant superior antitumour activity as compared to combined PTX treatment with radiation (P=0.0277). On the other hand, a histopathological study of lung sections revealed no significant difference in histopathological changes between mice treated with PTX and radiation and those treated with NK105 and radiation. Flow-cytometric analysis showed that NK105-treated LLC tumour cells showed more severe arrest at the G2/M phase as compared to PTX-treated tumour cells. The superior radiosensitising activity of NK105 was thus considered to be attributable to the more severe cell cycle arrest at the G2/M phase induced by NK105 as compared to that induced by free PTX. The present study results suggest that further clinical trials are warranted to determine the efficacy and feasibility of combined NK105 therapy with radiation.
authors.affiliation: Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Negishi
authors.forename: F
authors.initials: F
authors.lastname: Koizumi
authors.forename: H
authors.initials: H
authors.lastname: Uchino
authors.forename: J
authors.initials: J
authors.lastname: Kuroda
authors.forename: T
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: S
authors.initials: S
authors.lastname: Naito
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D000818:Animals; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D024061:Collagen Type III; C500671:NK105; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel