Fabrication of contrast agents for magnetic resonance imaging from polymer-brush-afforded iron oxide magnetic nanoparticles prepared by surface-initiated living radical polymerization.

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.

Blood clearance and biodistribution of polymer brush-afforded silica particles prepared by surface-initiated living radical polymerization.

The physiological properties of polymer brush-afforded silica particles prepared by surface-initiated living radical polymerization were investigated in terms of the circulation lifetime in the blood and distribution in tissues. Hydrophilic polymers consisting mainly of poly(poly(ethylene glycol) methyl ether methacrylate) were grafted onto silica particles by surface-initiated atom transfer radical polymerization that was mediated by a copper complex to produce hairy hybrid particles. A series of hybrid particles was synthesized by varying the diameter of the silica core and the chain length of the polymer brush to examine the relationship between their physicochemical and physiological properties. The hybrid particles were injected intravenously into mice to investigate systematically their blood clearance and body distribution. It was revealed that the structural features of the hybrid particles significantly affected their in vivo pharmacokinetics. Some hybrid particles exhibited an excellently prolonged circulation lifetime in the blood with a half life of ∼20 h. When such hybrid particles were injected intravenously into a tumor-bearing mouse, they preferentially accumulated in tumor tissue. The tumor-targeted delivery was optically visualized using hybrid particles grafted with fluorescence-labeled polymer brushes.