Fabrication of Contrast Agents for Magnetic ResonanceImaging from Polymer-Brush-Afforded Iron Oxide Magnetic NanoparticlesPrepared by Surface-Initiated Living Radical Polymerization.

Theaim of this study is to fabricate a contrast agent for magneticresonance imaging (MRI) by using hybrid particles composed of a coreof iron oxide magnetite (Fe3O4) nanoparticlesand a shell of hydrophilic polymer brush synthesized by surface-initiated(SI) living radical polymerization. To achieve this, Fe3O4nanoparticles were surface-modified with initiatinggroups for atom transfer radical polymerization (ATRP) via a ligand-exchangereaction in the presence of a triethoxysilane derivative having anATRP initiation site. The ATRP-initiator-functionalized Fe3O4nanoparticles were used for performing the SI-ATRPof methyl methacrylate to demonstrate the ability of the synthesizednanoparticles to produce well-defined polymer brushes on their surfaces.The polymerization proceeded in a living fashion so as to producegraft polymers with targeted molecular weights and narrow molecularweight distribution. The average graft density was estimated to beas high as 0.7 chains/nm2, which indicates the formationof so-called concentrated polymer brushes on the Fe3O4nanoparticles. Dynamic light scattering and transmissionelectron microscope observations of the hybrid nanoparticles revealedtheir uniformity and dispersibility in solvents to be excellent. Asimilar polymerization process was conducted using a hydrophilic monomer,poly(ethylene glycol) methyl ether methacrylate (PEGMA), to prepareFe3O4nanoparticles grafted with poly(PEGMA)brushes. The resultant hybrid nanoparticles showed excellent dispersibilityin aqueous media including physiological conditions without causingany aggregations. The blood clearance and biodistribution of the hybridparticles were investigated by intravenously injecting particles labeledwith a radio isotope, 125I, into mice. It was found thatsome hybrid particles exhibited an excellently prolonged circulationlifetime in the blood with a half-life of about 24 h. When such hybridparticles were injected intravenously into a tumor-bearing mouse,they preferentially accumulated in the tumor tissues owing to theso-called enhanced permeability and retention effect. The tumor-targeteddelivery was visualized by a T2-enhacedMRI measurement. [ABSTRACT FROM AUTHOR]