title: Fabrication of contrast agents for magnetic resonance imaging from polymer-brush-afforded iron oxide magnetic nanoparticles prepared by surface-initiated living radical polymerization.
abstract: The aim of this study is to fabricate a contrast agent for magnetic resonance imaging (MRI) by using hybrid particles composed of a core of iron oxide magnetite (Fe3O4) nanoparticles and a shell of hydrophilic polymer brush synthesized by surface-initiated (SI) living radical polymerization. To achieve this, Fe3O4 nanoparticles were surface-modified with initiating groups for atom transfer radical polymerization (ATRP) via a ligand-exchange reaction in the presence of a triethoxysilane derivative having an ATRP initiation site. The ATRP-initiator-functionalized Fe3O4 nanoparticles were used for performing the SI-ATRP of methyl methacrylate to demonstrate the ability of the synthesized nanoparticles to produce well-defined polymer brushes on their surfaces. The polymerization proceeded in a living fashion so as to produce graft polymers with targeted molecular weights and narrow molecular weight distribution. The average graft density was estimated to be as high as 0.7 chains/nm(2), which indicates the formation of so-called concentrated polymer brushes on the Fe3O4 nanoparticles. Dynamic light scattering and transmission electron microscope observations of the hybrid nanoparticles revealed their uniformity and dispersibility in solvents to be excellent. A similar polymerization process was conducted using a hydrophilic monomer, poly(ethylene glycol) methyl ether methacrylate (PEGMA), to prepare Fe3O4 nanoparticles grafted with poly(PEGMA) brushes. The resultant hybrid nanoparticles showed excellent dispersibility in aqueous media including physiological conditions without causing any aggregations. The blood clearance and biodistribution of the hybrid particles were investigated by intravenously injecting particles labeled with a radio isotope, (125)I, into mice. It was found that some hybrid particles exhibited an excellently prolonged circulation lifetime in the blood with a half-life of about 24 h. When such hybrid particles were injected intravenously into a tumor-bearing mouse, they preferentially accumulated in the tumor tissues owing to the so-called enhanced permeability and retention effect. The tumor-targeted delivery was visualized by a T2-enhaced MRI measurement.
authors: Institute for Chemical Research, Kyoto University , Uji, Kyoto 611-0011, Japan.
authors: Kohji
authors: K
authors: Ohno
authors: Chizuru
authors: C
authors: Mori
authors: Tatsuki
authors: T
authors: Akashi
authors: Shinichi
authors: S
authors: Yoshida
authors: Yoshiyuki
authors: Y
authors: Tago
authors: Yoshinobu
authors: Y
authors: Tsujii
authors: Yasuhiko
authors: Y
authors: Tabata
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003287:Contrast Media / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D005609:Free Radicals / Q000737:chemistry*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000175:diagnosis; D010316:Particle Size; D058105:Polymerization; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D005609:Free Radicals; D058185:Magnetite Nanoparticles; D011108:Polymers; C000499:ferric oxide