Novel therapeutic perspectives for wet age-related macular degeneration: RGD-modified liposomes loaded with 2-deoxy-D-glucose as a promising nanomedicine.

Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 8213295 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1950-6007 (Electronic) Linking ISSN: 07533322 NLM ISO Abbreviation: Biomed Pharmacother Subsets: MEDLINE

Publication: Paris : Editions Scientifiques Elsevier
Original Publication: New York, N.Y. : Masson Pub. USA, Inc., c1982-

Liposomes* ; Oligopeptides*/chemistry ; Nanomedicine*/methods ; Choroidal Neovascularization*/drug therapy ; Choroidal Neovascularization*/pathology ; Choroidal Neovascularization*/metabolism ; Wet Macular Degeneration*/drug therapy ; Wet Macular Degeneration*/metabolism ; Deoxyglucose*/pharmacology ; Deoxyglucose*/administration & dosage ; Vascular Endothelial Growth Factor Receptor-2*/metabolism; Animals ; Humans ; Human Umbilical Vein Endothelial Cells/metabolism ; Human Umbilical Vein Endothelial Cells/drug effects ; Mice ; Mice, Inbred C57BL ; Endothelial Cells/drug effects ; Endothelial Cells/metabolism

Choroidal neovascularization (CNV), characterized as a prominent feature of wet age-related macular degeneration (AMD), is a primary contributor to visual impairment and severe vision loss globally, while the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells is dictated by angiogenic growth factors alone. Even though treatments targeting vascular endothelial growth factor (VEGF), like Ranibizumab, are widely administered, more than half of the patients still exhibit inadequate or null responses, emphasizing the imperative need for solutions to this problem. Here, aiming to explore therapeutic strategies from a novel perspective of endothelial cell metabolism, a biocompatible nanomedicine delivery system is constructed by loading RGD peptide-modified liposomes with 2-deoxy-D-glucose (RGD@LP-2-DG). RGD@LP-2-DG displayed good targeting performance towards endothelial cells and excellent in vitro and in vivo inhibitory effects on neovascularization were demonstrated. Moreover, our mechanistic studies revealed that 2-DG interfered with N-glycosylation, leading to the inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream signaling. Notably, the remarkable inhibitory effect on neovascularization and biocompatibility of RGD@LP-2-DG render it a highly promising and clinically translatable therapeutic candidate for the treatment of wet AMD and other angiogenic diseases, particularly in patients who are unresponsive to currently available treatments.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Keywords: 2-deoxy-D-glucose; Choroidal neovascularization; N-glycosylation; Nanoliposome; RGD

0 (Liposomes)
0 (Oligopeptides)
78VO7F77PN (arginyl-glycyl-aspartic acid)
9G2MP84A8W (Deoxyglucose)
EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)

Date Created: 20240524 Date Completed: 20240602 Latest Revision: 20240610

20240610

10.1016/j.biopha.2024.116776

38788546