title: Hybrid Calcium Phosphate-Polymeric Micelles Incorporating Gadolinium Chelates for Imaging-Guided Gadolinium Neutron Capture Tumor Therapy.
abstract: Gadolinium (Gd) chelates-loaded nanocarriers have high potential for achieving magnetic resonance imaging (MRI)-guided Gd neutron capture therapy (GdNCT) of tumors. Herein, we developed calcium phosphate micelles hybridized with PEG-polyanion block copolymers, and incorporated with the clinical MRI contrast agent Gd-diethylenetriaminepentaacetic acid (Gd-DTPA/CaP). The Gd-DTPA/CaP were nontoxic to cancer cells at the concentration of 100 μM based on Gd-DTPA, while over 50% of the cancer cells were killed by thermal neutron irradiation at this concentration. Moreover, the Gd-DTPA/CaP showed a dramatically increased accumulation of Gd-DTPA in tumors, leading to the selective contrast enhancement of tumor tissues for precise tumor location by MRI. The enhanced tumor-to-blood distribution ratio of Gd-DTPA/CaP resulted in the effective suppression of tumor growth without loss of body weight, indicating the potential of Gd-DTPA/CaP for safe cancer treatment.
authors.affiliation: †Innovation Center of Nanomedicine, Kawasaki Institute of Industry Promotion, 66-20 Horikawa-cho, Saiwai-ku, Kawasaki 212-0013, Japan.|‡Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan.|§Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Peng
authors.initials: P
authors.lastname: Mi
authors.affiliation: ⊥Department of Nuclear Engineering and Management, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Novriana
authors.initials: N
authors.lastname: Dewi
authors.affiliation: ⊥Department of Nuclear Engineering and Management, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yanagie
authors.affiliation: ∥Molecular Imaging Center, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage, Chiba, 263-8555, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kokuryo
authors.affiliation: #Research Reactor Institute, Kyoto University, Asahiro nishi, Kumatori-cho, Sennan-gun, Osaka 590-0494, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: #Research Reactor Institute, Kyoto University, Asahiro nishi, Kumatori-cho, Sennan-gun, Osaka 590-0494, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sakurai
authors.affiliation: ∇Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Li
authors.affiliation: ∥Molecular Imaging Center, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage, Chiba, 263-8555, Japan.
authors.forename: Ichio
authors.initials: I
authors.lastname: Aoki
authors.affiliation: #Research Reactor Institute, Kyoto University, Asahiro nishi, Kumatori-cho, Sennan-gun, Osaka 590-0494, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
authors.affiliation: ⊥Department of Nuclear Engineering and Management, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: ∇Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Horacio
authors.initials: H
authors.lastname: Cabral
authors.affiliation: †Innovation Center of Nanomedicine, Kawasaki Institute of Industry Promotion, 66-20 Horikawa-cho, Saiwai-ku, Kawasaki 212-0013, Japan.|‡Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.affiliation: †Innovation Center of Nanomedicine, Kawasaki Institute of Industry Promotion, 66-20 Horikawa-cho, Saiwai-ku, Kawasaki 212-0013, Japan.|§Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.|∇Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.|⊗Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002614:Chelating Agents; D003287:Contrast Media; D019786:Gadolinium DTPA; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D057054:Molecular Imaging; D009369:Neoplasms / Q000175:diagnosis / Q000532:radiotherapy*; D017247:Neutron Capture Therapy; D011108:Polymers / Q000737:chemistry*
chemical_list: D002130:Calcium Phosphates; D002614:Chelating Agents; D003287:Contrast Media; D008823:Micelles; D011108:Polymers; C020243:calcium phosphate; D019786:Gadolinium DTPA
keywords: MRI; calcium phosphate micelle; drug delivery system; gadolinium neutron capture therapy