title: Thermoactivatable polymer-grafted liposomes for low-invasive image-guided chemotherapy.
abstract: The objective of this study was to develop a thermotriggered, polymer-based liposomal drug carrier with an activatable magnetic resonance imaging (MRI) contrast property for monitoring the release of substances and for localized tumor therapy. The multimodal thermoactivatable polymer-grafted liposomes (MTPLs) were tested to investigate whether the accumulation of MTPLs in colon-26 grafted tumors could be visualized in vivo using MRI and optical imaging, whether MTPLs induce signal enhancement, reflecting the release of their contents, after triggering by short-term heating (42.5°C for 10 minutes) 9 hours after MTPL administration (late-phase triggering), and whether MTPLs can provide a sufficient antitumor effect. The imaging and therapeutic properties of MTPLs were tested both in vitro and in vivo (BALB/c nude mice: heated group with MTPLs (n = 5), nonheated group with MTPLs (n = 5), heated group with doxorubicin-free MTPLs (n = 5), nonheated group with manganese-free MTPLs (n = 5), and kinetics observation group (n = 3); N = 23). Through in vivo MRI and fluorescent imaging, the MTPLs were shown to have significantly accumulated in the grafted colon-26 tumors 8 hours after administration. Delayed thermotriggering (9 hours after administration) caused MR signal enhancement, reflecting the release of their contents, after a short exposure to tolerable heat. In addition, significant antitumor effects were observed after treatment. The proposed polymer-based activatable MTPLs with a "delayed thermotrigger" provide a promising technology for cancer theranostics that allows minimal adverse effects and rapid interactive therapy.
authors: Molecular Imaging Center, National Institute of Radiological Sciences (NIRS), Chiba, Japan. Electronic address: aoki@nirs.go.jp.
authors: Ichio
authors: I
authors: Aoki
authors: Molecular Imaging Center, National Institute of Radiological Sciences (NIRS), Chiba, Japan.
authors: Misao
authors: M
authors: Yoneyama
authors: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Sakai, Japan.
authors: Jun
authors: J
authors: Hirose
authors: Department of Intractable Diseases, National Center for Global Health and Medicine, Tokyo, Japan.
authors: Yuzuru
authors: Y
authors: Minemoto
authors: Department of Intractable Diseases, National Center for Global Health and Medicine, Tokyo, Japan.
authors: Takayoshi
authors: T
authors: Koyama
authors: Molecular Imaging Center, National Institute of Radiological Sciences (NIRS), Chiba, Japan.
authors: Daisuke
authors: D
authors: Kokuryo
authors: Molecular Imaging Center, National Institute of Radiological Sciences (NIRS), Chiba, Japan.
authors: Rumiana
authors: R
authors: Bakalova
authors: Molecular Imaging Center, National Institute of Radiological Sciences (NIRS), Chiba, Japan.
authors: Shuhei
authors: S
authors: Murayama
authors: Molecular Imaging Center, National Institute of Radiological Sciences (NIRS), Chiba, Japan.
authors: Tsuneo
authors: T
authors: Saga
authors: Department of Macromolecular Science, Graduate School of Science, Osaka University, Toyonaka, Japan.
authors: Sadahito
authors: S
authors: Aoshima
authors: Department of Intractable Diseases, National Center for Global Health and Medicine, Tokyo, Japan.
authors: Yukihito
authors: Y
authors: Ishizaka
authors: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Sakai, Japan.
authors: Kenji
authors: K
authors: Kono
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D006801:Humans; D008081:Liposomes; D008279:Magnetic Resonance Imaging; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011108:Polymers / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D011108:Polymers