title: VCAM-1-targeting gold nanoshell probe for photoacoustic imaging of atherosclerotic plaque in mice.
abstract: The development of molecular probes and novel imaging modalities, allowing better resolution and specificity, is associated with an increased potential for molecular imaging of atherosclerotic plaques especially in basic and pre-clinical research applications. In that context, a photoacoustic molecular probe based on gold nanoshells targeting VCAM-1 in mice (immunonanoshells) was designed. The molecular probe was validated in vitro and in vivo, showing no noticeable acute toxic effects. We performed the conjugation of gold nanoshells displaying near-infrared absorption properties with VCAM-1 antibody molecules and PEG to increase their biocompatibility. The resulting immunonanoshells obtained under different conditions of conjugation were then assessed for specificity and sensitivity. Photoacoustic tomography was performed to determine the ability to distinguish gold nanoshells from blood both in phantoms and in vivo. Ex vivo optical projection tomography of hearts and aortas from atherosclerotic and control mice confirmed the selective accumulation of the immunonanoshells in atherosclerotic-prone regions in mice, thus validating the utility of the probe in vivo in small animals for pre-clinical research. These immunonanoshells represent an adequate mean to target atherosclerotic plaques in small animals, leading to new tools to follow the effect of therapies on the progression or regression of the disease.
authors.affiliation: Department of Electrical Engineering, École Polytechnique de Montréal, Canada.
authors.forename: Leonie
authors.initials: L
authors.lastname: Rouleau
authors.forename: Romain
authors.initials: R
authors.lastname: Berti
authors.forename: Vanessa W K
authors.initials: VW
authors.lastname: Ng
authors.forename: Carl
authors.initials: C
authors.lastname: Matteau-Pelletier
authors.forename: Tina
authors.initials: T
authors.lastname: Lam
authors.forename: Pierre
authors.initials: P
authors.lastname: Saboural
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Kakkar
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lesage
authors.forename: Eric
authors.initials: E
authors.lastname: Rhéaume
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D002461:Cell Line, Transformed; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D006046:Gold / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D057145:Nanoshells; D061088:Photoacoustic Techniques; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology; D041622:Tomography, Optical / Q000379:methods*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D019010:Vascular Cell Adhesion Molecule-1; D006046:Gold