title: Phosphatidylcholine-coated iron oxide nanomicelles for in vivo prolonged circulation time with an antibiofouling protein corona.
abstract: We report the synthesis of micellar phosphatidylcholine-coated superparamagnetic iron oxide nanoparticles as a new long circulation contrast agents for magnetic resonance imaging. Oleic acid-coated Fe3 O4 nanoparticles were first prepared through thermal degradation and then encapsulated into small clusters with a phosphatidylcholine coating to obtain hydrophilic nanomicelles. A thorough characterization confirmed the chemical nature of the coating and the excellent colloidal stability of these nanomicelles in aqueous media. Magnetization and relaxivity properties proved their suitability as magnetic resonance imaging (MRI) contrast agent and in vitro cell viability data showed low toxicity. Vascular lifetime and elimination kinetics in the liver were assessed by blood relaxometry and by in vivo MRI in rats and compared with "control" particles prepared with a polyethylene glycol derivative. These micellar particles had a lifetime in blood of more than 10 h, much longer than the control nanoparticles (≈2 h), which is remarkable considering that the coating molecule is a small biocompatible zwitterionic phospholipid. The protein corona was characterized after incubation with rat serum at different times by high-throughput proteomics, showing a higher proportion of bound apolipoproteins and other dysopsonins for the phosphatidylcholine particles. The antibiofouling properties of this corona and its resistance to the adsorption of proteins corroborate the observed enhanced stability and prolonged systemic circulation.
authors.affiliation: Advanced Imaging Unit, Department of Atherothrombosis, Imaging and Epidemiology, Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC) and CIBER de Enfermedades Respiratorias (CIBERES), Melchor Fernández Almagro, 3. 28029 Madrid (Spain).
authors.forename: Hugo
authors.initials: H
authors.lastname: Groult
authors.forename: Jesús
authors.initials: J
authors.lastname: Ruiz-Cabello
authors.forename: Ana Victoria
authors.initials: AV
authors.lastname: Lechuga-Vieco
authors.forename: Jesús
authors.initials: J
authors.lastname: Mateo
authors.forename: Marina
authors.initials: M
authors.lastname: Benito
authors.forename: Izaskun
authors.initials: I
authors.lastname: Bilbao
authors.forename: María Paz
authors.initials: MP
authors.lastname: Martínez-Alcázar
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Lopez
authors.forename: Jesús
authors.initials: J
authors.lastname: Vázquez
authors.forename: Fernando F
authors.initials: FF
authors.lastname: Herranz
mesh_terms: D000818:Animals; D002460:Cell Line; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics; D005290:Ferric Compounds / Q000097:blood / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D008810:Mice, Inbred C57BL; D008823:Micelles; D010713:Phosphatidylcholines / Q000097:blood / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D008823:Micelles; D010713:Phosphatidylcholines; C000499:ferric oxide
keywords: iron; magnetic properties; micelles; nanoparticles; proteins