One-Pot Synthesis of PEGylated Ultrasmall Iron-Oxide Nanoparticles and Their in Vivo Evaluation as Magnetic Resonance Imaging Contrast Agents

Abstract

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.

Maghemite Functionalization for Antitumor Drug Vehiculization

“…poly(ethylene glycol)) (Lutz et al, 2006), dextran or poly(vinyl alcohol) (Liu et al, 2008), or alternatively a layer containing metals (like gold (Jeong et al, 2006)), non-metals (like graphite (Seo et al, 2006)) or oxides (silica (Chastellain et al, 2004)) deposited on its surface. ii) Magnetic colloids may be encapsulated thanks to polymers which protect them from further cluster growth and keep them separated beyond the range of attractive forces (Arias et al, 2011b;Lecommandoux et al, 2006).…”

Thermoresponsive Polymers for Biomedical Applications

“…Much work has been done on the modification of inorganic particles with thermoresponsive polymers [148][149][150][151][152][153][154]. Zhang et al coated insoluble nanoparticles with PNIPAAm rendering them stable in aqueous solutions with temperature dependant solution properties and suggested uses in drug delivery and biological sensing [148].…”

Dual-Responsive Magnetic Core–Shell Nanoparticles for Nonviral Gene Delivery and Cell Separation

“…In this case, the initiating moiety is immobilized on the nanoparticle surface and the polymerization takes place directly from the surface. 1,2 We present the synthesis of core-shell NPs via the grafting-from approach utilizing a dopamine based ATRP initiator. Dopamine is considered to be a robust anchor for iron oxide surfaces in aqueous media.…”