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.

Targeting cell adhesion molecules with nanoparticles usingin vivoand flow-basedin vitromodels of atherosclerosis

“…Rouleau et al synthesized gold nanoshell VCAM-1-targeted photoacoustic probes, known as immunonanoshells. 55 These immunonanoshells accumulated in VCAM-1 expressing atherosclerotic lesions of ApoE À/À mice by PAT. Ex vivo optical projection tomography of excised aorta confirmed this result, showing enhanced MR contrast.…”

Photothermal response of hollow gold nanoshell to laser irradiation: Continuous wave, short and ultrashort pulse

“…In this case, AuNSs dissipate the absorbed energy into their surrounding environment without a substantial increase of their temperature [22,23]. Some applications such as photoacoustic imaging of cells and gene silencing by transfection, necessitate a much higher energy density in the vicinity of the AuNSs [24]. Further reducing of the pulse width up to fs regime enables a very high-localized temperature increase, more efficient energy deposition allowing the cleavage of bonds to link molecules to the AuNS surface [25].…”

Utility of models of the gastrointestinal tract for assessment of the digestion and absorption of engineered nanomaterials released from food matrices

“…X-ray computed tomography and NIR fluorescent imaging can also detect NPs such as fluorescent silica-coated gold nanorods (Luo et al, 2011). Metallic nanoshells can be visualized inside a tissue in vivo and ex vivo with a photoacoustic molecular probe and optical projection tomography (Rouleau et al, 2013), and nearinfrared similarly detects the biodistribution of gold and zinc oxide NPs deep in tissues (Lee et al, 2012). With cultured cells, the amount of fluorescently coated iron oxide nanomaterials taken up has been detected by flow cytometry (Wang et al, 2012).…”