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F. R. Haselton, P. K. Russ, A. Jayagopal; Nanotechnology - Guided Imaging and Therapy of Retinal Vascular Disease. Invest. Ophthalmol. Vis. Sci. 2010;51(13):424.
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Endothelial dysfunction is a common component of vascular diseases. The expression of numerous inflammatory endothelial biomarkers in these diseases offer significant nanomedicine-based diagnostic and therapeutic opportunities. In this study, we investigated the expression profile of inflammatory biomarkers in the ApoE-/- mouse model of atherosclerosis using targeted quantum dot (QD) nanocrystals. Additionally, we developed polymer-based targeted therapeutic nanocarriers directed toward several of these biomarkers, to validate diagnostic targets as potential portals for drug delivery.
We performed bioimaging of ApoE-/- and age-matched mice using a multispectral retinal fluorescence imaging system. Atheroma components in retinal and aortic tissues including cell adhesion molecules and integrins were analyzed using detection of targeted QD as well as conventional methods. Polymer-based nanocarriers directed against inflammatory biomarkers via antibodies or peptides were complexed with dye-labeled siRNA as a prototype cargo. Uptake of nanocarriers and therapeutic efficacy was quantified using fluorescence imaging and established molecular biology techniques.
Several biomarkers were upregulated in both retinal and aortic vasculature of ApoE-/-, but not in wild-type controls, such as vascular cell adhesion molecule (VCAM-1) and intercellular adhesion molecule (ICAM-1). These biomarkers were successfully imaged in the retinal vasculature in early and late atherosclerosis. Polymer nanocarriers targeted toward these cell adhesion molecules were capable of delivering functional siRNA within inflamed retinal endothelium in vitro and in vivo.
Our findings indicate that the retinal vasculature serves as a useful window for the imaging of vascular disease markers, including non-ocular vascular diseases. Furthermore, many of these targets feature not only diagnostic value but therapeutic potential, as they can be used as portals for drug delivery and gene therapy.
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