Phosphatidylcholine‐Coated Iron Oxide Nanomicelles for In Vivo Prolonged Circulation Time with an Antibiofouling Protein Corona |
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Authors: | Hugo Groult Dr Jesús Ruiz‐Cabello Ana Victoria Lechuga‐Vieco Dr Jesús Mateo Dr Marina Benito Izaskun Bilbao Dr María Paz Martínez‐Alcázar Dr Juan Antonio Lopez Dr Jesús Vázquez Dr Fernando F Herranz |
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Institution: | 1. 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);2. Universidad Complutense de Madrid (UCM), Plaza Ramón y Cajal s/n Ciudad Universitaria, 8040 Madrid (Spain);3. Chemistry Department, Analytical Chemistry Section, Facultad de Farmacia, Universidad CEU‐San Pablo, Urbanización Montepríncipe, Boadilla del Monte, 28660 Madrid (Spain);4. Proteomics Unit and Cardiovascular Proteomics Laboratory, Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3. 28029 Madrid (Spain) |
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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 Fe3O4 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. |
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Keywords: | iron magnetic properties micelles nanoparticles proteins |
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