One-pot synthesis of pegylated ultrasmall iron-oxide nanoparticles and their in vivo evaluation as magnetic resonance imaging contrast agents.
A well-defined copolymer poly(oligo(ethylene glycol) methacrylate-co-methacrylic acid) P(OEGMA-co-MAA) was studied as a novel water-soluble biocompatible coating for superparamagnetic iron oxide nanoparticles. This copolymer was prepared via a two-step procedure: a well-defined precursor poly(oligo(ethylene glycol) methacrylate-co-tert-butyl methacrylate), P(OEGMA-co-tBMA) (M(n) = 17300 g mol(-1); M(w)/M(n) = 1.22), was first synthesized by atom-transfer radical polymerization in the presence of the catalyst system copper(I) chloride/2,2'-bipyridyl and subsequently selectively hydrolyzed in acidic conditions. The resulting P(OEGMA-co-MAA) was directly utilized as a polymeric stabilizer in the nanoparticle synthesis. Four batches of ultrasmall PEGylated magnetite nanoparticles (i.e., with an average diameter below 30 nm) were prepared via aqueous coprecipitation of iron salts in the presence of variable amounts of P(OEGMA-co-MAA). The diameter of the nanoparticles could be easily tuned in the range 10-25 nm by varying the initial copolymer concentration. Moreover, the formed PEGylated ferrofluids exhibited a long-term colloidal stability in physiological buffer and could therefore be studied in vivo by magnetic resonance (MR) imaging. Intravenous injection into rats showed no detectable signal in the liver within the first 2 h. Maximum liver accumulation was found after 6 h, suggesting a prolongated circulation of the nanoparticles in the bloodstream as compared to conventional MR imaging contrast agents.
Lutz
Jean-François
JF
Research Group Nanotechnology for Life Science, Fraunhofer Institute for Applied Polymer Research, Geiselbergstrasse 69, Potsdam 14476, Germany.
Stiller
Sabrina
S
Hoth
Ann
A
Kaufner
Lutz
L
Pison
Ulrich
U
Cartier
Régis
R
D000818:Animals; D002850:Chromatography, Gel; D003287:Contrast Media / Q000138:chemical synthesis*; D004353:Drug Evaluation, Preclinical; D005290:Ferric Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006868:Hydrolysis; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide; D011092:Polyethylene Glycols