title: Thermal- and pH-Dependent Size Variable Radical Nanoparticles and Its Water Proton Relaxivity for Metal-Free MRI Functional Contrast Agents.
abstract: For development of the metal-free MRI contrast agents, we prepared the supra-molecular organic radical, TEMPO-UBD, carrying TEMPO radical, as well as the urea, alkyl group, and phenyl ring, which demonstrate self-assembly behaviors using noncovalent bonds in an aqueous solution. In addition, TEMPO-UBD has the tertiary amine and the oligoethylene glycol chains (OEGs) for the function of pH and thermal responsiveness. By dynamic light scattering and transmission electron microscopy imaging, the resulting self-assembly was seen to form the spherical nanoparticles 10-150 nm in size. On heating, interestingly, the nanoparticles showed a lower critical solution temperature (LCST) behavior having two-step variation. This double-LCST behavior is the first such example among the supra-molecules. To evaluate of the ability as MRI contrast agents, the values of proton ((1)H) longitudinal relaxivity (r1) were determined using MRI apparatus. In conditions below and above CAC at pH 7.0, the distinguishable r1 values were estimated to be 0.17 and 0.21 mM(-1) s(1), indicating the suppression of fast tumbling motion of TEMPO moiety in a nanoparticle. Furthermore, r1 values became larger in the order of pH 7.0 > 9.0 > 5.0. Those thermal and pH dependencies indicated the possibility of metal-fee MRI functional contrast agents in the future.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University , 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Morishita
authors.affiliation: Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences (NIRS), QST , Anagawa 4-9-1, Inage, Chiba-city 263-8555, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Murayama
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University , 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Araki
authors.affiliation: Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences (NIRS), QST , Anagawa 4-9-1, Inage, Chiba-city 263-8555, Japan.
authors.forename: Ichio
authors.initials: I
authors.lastname: Aoki
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University , 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.|PRESTO, Japan Science and Technology Agency , Kawaguchi 332-0012, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Karasawa
mesh_terms: D003287:Contrast Media / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging / Q000379:methods*; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D011522:Protons; D013696:Temperature; D014867:Water
chemical_list: D003287:Contrast Media; D011522:Protons; D014867:Water