Hennig, Robert and Ohlmann, Andreas and Staffel, Janina and Pollinger, Klaus and Haunberger, Alexandra and Breunig, Miriam and Schweda, Frank and Tamm, Ernst R. and Goepferich, Achim (2015) Multivalent nanoparticles bind the retinal and choroidal vasculature. JOURNAL OF CONTROLLED RELEASE, 220. pp. 265-274. ISSN 0168-3659, 1873-4995
Full text not available from this repository. (Request a copy)Abstract
The angiotensin II receptor type 1 (AT(1)R), which is expressed in blood vessels of the posterior eye, is of paramount significance in the pathogenesis of severe ocular diseases such as diabetic retinopathy and age-related macular degeneration. However, small molecule angiotensin receptor blockers (ARBs) have not proven to be a significant therapeutic success. We report here on a nanoparticle system consisting of ARB molecules presented in a multivalent fashion on the surface of quantum dots (Qdots). As a result of the multivalent receptor binding, nanoparticles targeted cellswith high AT(1)R expression and inhibited their angiotensin receptor signaling with an IC50 of 3.8 nM while showing only minor association to cells with low AT(1)R expression. After intravenous injection into the tail vein of mice, multivalent nanoparticles accumulated in retinal and choroidal blood vessels of the posterior eye. At the same time, multivalent ligand display doubled the Qdot concentration in the blood vessels compared to non-targeted Qdots. Remarkably, ARB-targeted Qdots showed no pronounced accumulation in AT(1)R-expressing off-target tissues such as the kidney. Following systemic application, this multivalent targeting approach has the potential to amplify AT(1)R blockade in the eye and concomitantly deliver a therapeutic payload into ocular lesions. (C) 2015 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANGIOTENSIN-II; QUANTUM DOTS; IN-VIVO; INTRAVENOUS-INJECTION; DIABETIC-RETINOPATHY; ENDOTHELIAL-CELLS; RECEPTOR BLOCKADE; NEOVASCULARIZATION; INFLAMMATION; CANDESARTAN; Multivalency; EXP3174; Quantum dots; Age-related macular degeneration; Diabetic retinopathy; Angiotensin II |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie Biology, Preclinical Medicine > Institut für Anatomie Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Apr 2019 07:08 |
| Last Modified: | 29 Apr 2019 07:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4270 |
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