title: Evaluation of thermo-triggered drug release in intramuscular-transplanted tumors using thermosensitive polymer-modified liposomes and MRI.
abstract: Multi-modal thermo-sensitive polymer-modified liposomes (MTPLs) containing an anticancer drug, MR contrast agent, and fluorescent dye have been investigated as "theranostic" nanodevices that can be used to monitor drug delivery in cancer therapy. Here, we measured the physical characteristics of MTPLs, observed the dynamics of MTPLs in vivo, visualized heat-triggered drug release using MRI, and evaluated the treatment effects of the MTPLs with and without heating. In vitro experiments demonstrated that the MTPLs released drugs at temperatures above 41°C. In vivo MTPLs accumulated in tumor tissue, with the accumulation maximized for 4-12hours. MR signal in the tumor was significantly elevated after mild heating for 15 minutes, indicating release of the contrast agent from the MTPLs was facilitated by heat-triggering. Tumor size after treatment with MTPLs and heating was significantly smaller than those of the control groups. In conclusion, MTPLs with MRI are useful for low-invasive cancer theranostics.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kokuryo
authors.affiliation: Graduate School of Engineering, Osaka Prefecture University, Sakai, Osaka, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Nakashima
authors.affiliation: Graduate School of Engineering, Osaka Prefecture University, Sakai, Osaka, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Ozaki
authors.affiliation: Graduate School of Engineering, Osaka Prefecture University, Sakai, Osaka, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Yuba
authors.affiliation: Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Singapore, Singapore.
authors.forename: Kai-Hsiang
authors.initials: KH
authors.lastname: Chuang
authors.affiliation: Graduate School of Science, Osaka University, Osaka, Japan.
authors.forename: Sadahito
authors.initials: S
authors.lastname: Aoshima
authors.affiliation: Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Ishizaka
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Saga
authors.affiliation: Graduate School of Engineering, Osaka Prefecture University, Sakai, Osaka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kono
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan. Electronic address: aoki@nirs.go.jp.
authors.forename: Ichio
authors.initials: I
authors.lastname: Aoki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D006358:Hot Temperature; D008081:Liposomes / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D011108:Polymers / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D005456:Fluorescent Dyes; D008081:Liposomes; D011108:Polymers; D004317:Doxorubicin
keywords: Drug targeting tumor therapeutics; Liposome; MRI; Thermo-sensitive polymer; Thermo-triggering