title: Surface-Functionalized Nanoparticles by Olefin Metathesis: A Chemoselective Approach for In Vivo Characterization of Atherosclerosis Plaque.
abstract: The use of click chemistry reactions for the functionalization of nanoparticles is particularly useful to modify the surface in a well-defined manner and to enhance the targeting properties, thus facilitating clinical translation. Here it is demonstrated that olefin metathesis can be used for the chemoselective functionalization of iron oxide nanoparticles with three different examples. This approach enables, in one step, the synthesis and functionalization of different water-stable magnetite-based particles from oleic acid-coated counterparts. The surface of the nanoparticles was completely characterized showing how the metathesis approach introduces a large number of hydrophilic molecules on their coating layer. As an example of the possible applications of these new nanocomposites, a focus was taken on atherosclerosis plaques. It is also demonstrated how the in vitro properties of one of the probes, particularly its Ca(2+) -binding properties, mediate their final in vivo use; that is, the selective accumulation in atherosclerotic plaques. This opens promising new applications to detect possible microcalcifications associated with plaque vulnerability. The accumulation of the new imaging tracers is demonstrated by in vivo magnetic resonance imaging of carotids and aorta in the ApoE(-/-) mouse model and the results were confirmed by histology.
authors.affiliation: Advanced Imaging Unit, Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC) and CIBER de enfermedades respiratorias(CIBERES), C/Melchor Fernández-Almagro 3. 28029 Madrid (Spain).|Universidad Complutense de Madrid, Plaza Ramón y Cajal, 28040 Madrid (Spain).
authors.forename: Beatriz
authors.initials: B
authors.lastname: Salinas
authors.affiliation: Advanced Imaging Unit, Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC) and CIBER de enfermedades respiratorias(CIBERES), C/Melchor Fernández-Almagro 3. 28029 Madrid (Spain).|Universidad Complutense de Madrid, Plaza Ramón y Cajal, 28040 Madrid (Spain).
authors.forename: Jesús
authors.initials: J
authors.lastname: Ruiz-Cabello
authors.affiliation: Advanced Imaging Unit, Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC) and CIBER de enfermedades respiratorias(CIBERES), C/Melchor Fernández-Almagro 3. 28029 Madrid (Spain).
authors.forename: Ana V
authors.initials: AV
authors.lastname: Lechuga-Vieco
authors.affiliation: Advanced Imaging Unit, Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC) and CIBER de enfermedades respiratorias(CIBERES), C/Melchor Fernández-Almagro 3. 28029 Madrid (Spain).
authors.forename: Marina
authors.initials: M
authors.lastname: Benito
authors.affiliation: Advanced Imaging Unit, Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC) and CIBER de enfermedades respiratorias(CIBERES), C/Melchor Fernández-Almagro 3. 28029 Madrid (Spain). fherranz@cnic.es.
authors.forename: Fernando
authors.initials: F
authors.lastname: Herranz
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D000818:Animals; D001011:Aorta / Q000737:chemistry* / Q000473:pathology*; D050197:Atherosclerosis / Q000175:diagnosis / Q000473:pathology*; D057930:Click Chemistry; D003287:Contrast Media; D005290:Ferric Compounds / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D058226:Plaque, Atherosclerotic / Q000737:chemistry* / Q000473:pathology*
chemical_list: D000475:Alkenes; D003287:Contrast Media; D005290:Ferric Compounds
keywords: atherosclerosis; imaging agents; iron oxide; nanoparticles; olefin metathesis