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Richard M. Awdeh, Shradha Prabhulkar, Adam de la Zerda, Sanjiv Gambhir; Development Of Functionalized Gold Nanoparticles As Diagnostic And Therapeutic Agents For Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2012;53(14):301.
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© ARVO (1962-2015); The Authors (2016-present)
Molecular in vivo imaging allows for diagnostic imaging, target screening, and therapeutic monitoring of disease on a molecular level, prior to evidence of pathologic changes that can be detected with conventional imaging modalities. Optical Coherence Tomography (OCT) is an imaging modality used to visualize ocular structures with high spatial resolution. We have created optimized gold nanoparticles (GNPs) which produce a strong OCT signal, beyond the background tissue OCT signal, and can fulfill the role of an exogenous OCT contrast agent. In order to achieve molecular diagnostic and therapeutic capabilities, we functionalized these GNPs with anti-VEGF antibodies, allowing for the dual purpose of molecular diagnostic imaging and therapy towards age-related macular degeneration (AMD).
GNPs with a longitudinal plasmon resonance at 840nm were synthesized using seed-mediated growth mechanism. The GNPs were covalently attached to anti-VEGF antibodies via carbodiimide chemistry. The anti-VEGF functionalized GNP constructs were tested in vivo in a laser induced mouse model of choroidal neovascularization. Tail-vein, venous sinus, intravitreal, and sub-retinal administration routes were tested to determine the optimal delivery technique. OCT images of the control (CNV induced mice with saline injections) and test groups (CNV induced mice with anti-VEGF functionalized GNPs) were acquired following injection to determine the localization dynamics of the GNP construct in this CNV mouse model.
OCT imaging reveals that there is a marked increment in the scattering intensity of areas around the laser induced lesions in anti-VEGF functionalized GNP injected mice versus the control group using tail vein injections. The minimal detectable concentration the systemic administration of these functionalized GNPs was 87nM in this set of experiments. These detection limits are in line with our published minimal detectable threshold of GNPs as low as 370pM for nonfunctionalized, locally administered GNPs in the eye.
Based on this data, we conclude that our antibody functionalized GNPs can be used with high-resolution, spectral-domain OCT for the molecular in vivo detection of AMD. Our future efforts will focus on the quantitative analysis of disease burden based on in vivo molecular profiling.
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