title: Hydrothermally synthesized PEGylated calcium phosphate nanoparticles incorporating Gd-DTPA for contrast enhanced MRI diagnosis of solid tumors.
abstract: Organic-inorganic hybrid nanoparticles with calcium phosphate (CaP) core and PEGylated shell were developed to incorporate magnetic resonance imaging (MRI) contrast agent diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) for noninvasive diagnosis of solid tumors. A two-step preparation method was applied to elaborate hybrid nanoparticles with a z-average hydrodynamic diameter about 80nm, neutral surface ξ-potential and high colloidal stability in physiological environments by self-assembly of poly(ethylene glycol)-b-poly(aspartic acid) block copolymer, Gd-DTPA, and CaP in aqueous solution, followed with hydrothermal treatment. Incorporation into the hybrid nanoparticles allowed Gd-DTPA to show significant enhanced retention ratio in blood circulation, leading to high accumulation in tumor positions due to enhanced permeability and retention (EPR) effect. Moreover, Gd-DTPA revealed above 6 times increase of relaxivity in the nanoparticle system compared to free form, and eventually, selective and elevated contrast enhancements in the tumor positions were observed. These results indicate the high potential of Gd-DTPA-loaded PEGylated CaP nanoparticles as a novel contrast agent for noninvasive cancer diagnosis.
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan.
authors.forename: Peng
authors.initials: P
authors.lastname: Mi
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: 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: Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kumagai
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: Takahiro
authors.initials: T
authors.lastname: Nomoto
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: SPring 8, JASRI, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5198, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Terada
authors.affiliation: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kishimura
authors.affiliation: Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan. Electronic address: nishiyama@res.titech.ac.jp.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan. Electronic address: kataoka@bmw.t.u-tokyo.ac.jp.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D001682:Biological Availability; D002130:Calcium Phosphates / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D019786:Gadolinium DTPA / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D006358:Hot Temperature; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D002130:Calcium Phosphates; D003287:Contrast Media; D004337:Drug Carriers; D011092:Polyethylene Glycols; C020243:calcium phosphate; D019786:Gadolinium DTPA
keywords: Block copolymer; Calcium phosphate nanoparticles; Cancer diagnosis; Gd-DTPA; Hydrothermal synthesis; MRI