Endothelial Protein C-Targeting Liposomes Show Enhanced Uptake and Improved Therapeutic Efficacy in Human Retinal Endothelial Cells
| Autor: | Michael Larsen, Andrew J. Urquhart, Thomas Lars Andresen, Fredrik Melander, Paul J. Kempen, Anthoula Arta, Anne Zebitz Eriksen |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Angiogenesis Cell Survival Endothelial cells Prednisolone Blotting Western Retina Flow cytometry 03 medical and health sciences EPCR Drug Delivery Systems SDG 3 - Good Health and Well-being Cell Movement medicine Corticosteroids Humans Glucocorticoids Cells Cultured Cell Proliferation Tube formation Endothelial protein C receptor Liposome Microscopy Confocal medicine.diagnostic_test Neovascularization Pathologic Cell growth Chemistry Endothelial Cells Endothelial Protein C Receptor Retinal Vessels Flow Cytometry In vitro Cell biology Endothelial stem cell 030104 developmental biology Liposomes Cytokines |
| Zdroj: | Arta, A, Eriksen, A Z, Melander, F, Kempen, P, Larsen, M, Andresen, T L & Urquhart, A J 2018, ' Endothelial protein C–targeting liposomes show enhanced uptake and improved therapeutic efficacy in human retinal endothelial cells ', Investigative Ophthalmology and Visual Science, vol. 59, no. 5, pp. 2119-2132 . https://doi.org/10.1167/iovs.18-23800 Arta, A, Eriksen, A Z, Melander, F, Kempen, P, Larsen, M, Andresen, T L & Urquhart, A J 2018, ' Endothelial Protein C–Targeting Liposomes Show Enhanced Uptake and Improved Therapeutic Efficacy in Human Retinal Endothelial Cells ', Investigative Ophthalmology & Visual Science, vol. 59, no. 5, pp. 2119-2132 . https://doi.org/10.1167/iovs.18-23800 |
| ISSN: | 1552-5783 |
| Popis: | PURPOSE. To determine whether human retinal endothelial cells (HRECs) express the endothelial cell protein C receptor (EPCR) and to realize its potential as a targeting moiety by developing novel single and dual corticosteroid–loaded functionalized liposomes that exhibit both enhanced uptake by HRECs and superior biologic activity compared to nontargeting liposomes and free drug.METHODS. EPCR expression of HRECs was investigated through flow cytometry and Western blot assays. EPCR-targeting liposomes were developed by functionalizing EPCR-specific antibodies onto liposomes, and the uptake of liposomes was assessed with flow cytometry and confocal laser scanning microscopy. The therapeutic potential of EPCR-targeting liposomes was determined by loading them with prednisolone either through bilayer insertion and/or by remote loading into the aqueous core. The carrier efficacy was assessed in two ways through its ability to inhibit secretion of interleukins in cells stimulated with high glucose and angiogenesis in vitro by using an endothelial cell tube formation assay.RESULTS. HRECs express EPCR at a similar level in both human aortic and umbilic vein endothelial cells. The EPCR-targeting liposomes displayed at least a 3-fold higher uptake compared to nontargeting liposomes. This enhanced uptake was translated into superior antiinflammatory efficacy, as the corticosteroid-loaded EPCR-targeting liposomes significantly reduced the secretion of IL-8 and IL-6 and inhibited the development of cell tube formations in contrast to nontargeting liposomes.CONCLUSIONS. We show that HRECs express EPCR and this receptor could be a promising nanomedicine target in ocular diseases where the endothelial barrier of the retina is compromised. |
| Databáze: | OpenAIRE |
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