Hennig, Robert and Kuespert, Sabrina and Haunberger, Alexandra and Goepferich, Achim and Fuchshofer, Rudolf (2016) Cyclic RGD peptides target human trabecular meshwork cells while ameliorating connective tissue growth factor-induced fibrosis. JOURNAL OF DRUG TARGETING, 24 (10). pp. 952-959. ISSN 1061-186X, 1029-2330
Full text not available from this repository. (Request a copy)Abstract
The major risk factor for primary open-angle glaucoma is increased intraocular pressure stemming from elevated outflow resistance in the trabecular meshwork (TM) region. Integrins play a pivotal role in the TM by influencing its biological properties and growth factor signaling. Pathologic changes in the TM are partially mediated by growth factors like connective tissue growth factor (CTGF). Specific targeting of TM cells could play a critical clinical role by increasing the therapeutic efficacy of nanoparticles, e.g. for nonviral gene delivery. Quantum dots with cyclo(RGDfC) covalently immobilized to their surface effectively targeted cultured TM cells and were rapidly and efficiently endocytosed by binding to alpha(v)beta(3) and alpha(v)beta(5) integrins. Compared to the integrin-overexpressing U87-MG cell line, the association of RGD-modified nanoparticles with the TM cells was significantly higher. Binding and uptake into TM cells was receptor-mediated and suppressible with free peptide. Soluble cyclic RGD peptides effectively attenuated CTGF-mediated effects and inhibited CTGF signaling. Due to their antagonism for alpha(v)beta(3) and alpha(v)beta(5) integrins, these cyclic RGD pentapeptides effectively ameliorated the CTGF-induced effects and strongly promoted specific nanoparticle association. Thus, cyclic RGD peptides are powerful multifunctional ligands for both addressing nanomaterials to the TM and interfering with pathologic CTGF signaling upon arrival.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEPATIC STELLATE CELLS; AQUEOUS-HUMOR; GLAUCOMATOUS EYES; NONVIRAL VECTORS; GENE DELIVERY; FUNCTIONALIZED NANOPARTICLES; INTEGRIN ALPHA(V)BETA(3); ALPHA-V-BETA-3 INTEGRIN; ENDOTHELIAL-CELLS; OUTFLOW FACILITY; alpha v beta 3 integrin; active targeting; CTGF; cyclo(RGDfC); gene delivery; glaucoma; nanoparticles; quantum dots; receptor-mediated endocytosis |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Mar 2019 13:44 |
| Last Modified: | 18 Mar 2019 13:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2587 |
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