Pollinger, Klaus and Hennig, Robert and Ohlmann, Andreas and Fuchshofer, Rudolf and Wenzel, Rebecca and Breunig, Miriam and Tessmar, Joerg and Tamm, Ernst R. and Goepferich, Achim (2013) Ligand-functionalized nanoparticles target endothelial cells in retinal capillaries after systemic application. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 110 (15). pp. 6115-6120. ISSN 0027-8424,
Full text not available from this repository. (Request a copy)Abstract
To date, diseases affecting vascular structures in the posterior eye are mostly treated by laser photocoagulation and multiple intraocular injections, procedures that destroy healthy tissue and can cause vision-threatening complications. To overcome these drawbacks, we investigate the feasibility of receptor-mediated nanoparticle targeting to capillary endothelial cells in the retina after i.v. application. Cell-binding studies using microvascular endothelial cells showed receptor-specific binding and cellular uptake of cyclo(RGDfC)-modified quantum dots via the alpha v beta 3 integrin receptor. Conversely, Mueller cells and astrocytes, representing off-target cells located in the retina, revealed only negligible interaction with nanoparticles. In vivo experiments, using nude mice as the model organism, demonstrated a strong binding of the ligand-modified quantum dots in the choriocapillaris and intraretinal capillaries upon i.v. injection and 1-h circulation time. Nontargeted nanoparticles, in contrast, did not accumulate to a significant amount in the target tissue. The presented strategy of targeting integrin receptors in the retina could be of utmost value for future intervention in pathologies of the posterior eye, which are to date only accessible with difficulty.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | QUANTUM DOTS; DIABETIC-RETINOPATHY; CHOROIDAL NEOVASCULARIZATION; INTRAVITREAL TRIAMCINOLONE; ALPHA-V-BETA-3 INTEGRIN; MACULAR DEGENERATION; TUMOR VASCULATURE; MULLER CELLS; IN-VIVO; ANGIOGENESIS; age-related macular degeneration; diabetic retinopathy; choroid; neovascularization; ligand receptor interaction |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 615 Pharmacy |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie > Prof. Dr. Ernst Tamm Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Apr 2020 05:56 |
| Last Modified: | 17 Apr 2020 05:56 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16830 |
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