April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Targeted Nanocarriers for Therapy of Ocular Neovascularization
Author Affiliations & Notes
  • Ashwath Jayagopal
    Chemistry, Ophthalmology, Vanderbilt University, Nashville, Tennessee
  • Joshua M. Barnett
    Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Nashville, Tennessee
  • John S. Penn
    Vanderbilt Eye Institute, Vanderbilt Univ Schl of Med, Nashville, Tennessee
  • Footnotes
    Commercial Relationships  Ashwath Jayagopal, None; Joshua M. Barnett, None; John S. Penn, None
  • Footnotes
    Support  Knights Templar Eye Foundation, International Retinal Research Foundation, Vanderbilt Institute of Chemical Biology
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4844. doi:
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      Ashwath Jayagopal, Joshua M. Barnett, John S. Penn; Targeted Nanocarriers for Therapy of Ocular Neovascularization. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4844.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Cell adhesion molecules (CAMs), particularly ICAM-1 and VCAM-1, are markers of inflammation expressed on retinal endothelial cell surfaces in a broad spectrum of ocular vascular diseases, including retinal neovascularization, and therefore constitute potential targets for promoting homing, binding, and internalization of nanoscale agents. We have developed a series of nanocarriers targeted against CAMs which can bear imaging or therapeutic payloads and deliver them to the cytoplasm of dysfunctional endothelial cells. The goal of this study was to demonstrate the utility of CAM targeted nanocarriers for intracellular delivery of antiangiogenic siRNA in two rat models of retinal neovascularization.

Methods: : CAM targeted nanocarriers bearing VEGFR2 and other siRNAs were characterized to determine optimal size, surface charge, and encapsulation efficiencies. Cytotoxicity, delivery efficiency, and functional knockdown of several molecular targets were determined in retinal microvascular endothelial cells. Biodistribution and efficacy of nanocarriers in animal models of neovascular age-related macular degeneration and oxygen-induced retinopathy were analyzed.

Results: : CAM targeted nanocarriers were capable of specific targeting of the CAMs ICAM-1 and VCAM-1 on inflamed retinal endothelial cells in vitro and in vivo. Specific targeting of inflamed retinal endothelium was observed in both animal models of vascular disease, using CAMs on neovessel endothelial cells as a portal for delivery of therapies. Knockdown of several molecular targets via siRNAs was achieved in vitro and in vivo.

Conclusions: : CAM targeted nanocarriers are a promising framework for the delivery of diverse imaging and therapeutic payloads to the cytoplasm of diseased retinal endothelial cells in vivo.

Keywords: neovascularization • gene transfer/gene therapy • retina 

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