Ocular Wnt/β-Catenin Pathway Inhibitor XAV939-Loaded Liposomes for Treating Alkali-Burned Corneal Wound and Neovascularization

Corneal wound involves a series of complex and coordinated physiological processes, leading to persistent epithelial defects and opacification. An obstacle in the treatment of ocular diseases is poor drug delivery and maintenance. In this study, we constructed a Wnt/β-catenin pathway inhibitor, XAV9...

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Main Authors: Yueyang Zhong, Kai Wang, Yin Zhang, Qichuan Yin, Su Li, Jiaming Wang, Xiaobo Zhang, Haijie Han, Ke Yao
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-10-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2021.753879/full
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author Yueyang Zhong
Yueyang Zhong
Kai Wang
Kai Wang
Yin Zhang
Yin Zhang
Qichuan Yin
Qichuan Yin
Su Li
Su Li
Jiaming Wang
Xiaobo Zhang
Xiaobo Zhang
Haijie Han
Haijie Han
Ke Yao
Ke Yao
author_facet Yueyang Zhong
Yueyang Zhong
Kai Wang
Kai Wang
Yin Zhang
Yin Zhang
Qichuan Yin
Qichuan Yin
Su Li
Su Li
Jiaming Wang
Xiaobo Zhang
Xiaobo Zhang
Haijie Han
Haijie Han
Ke Yao
Ke Yao
author_sort Yueyang Zhong
collection DOAJ
description Corneal wound involves a series of complex and coordinated physiological processes, leading to persistent epithelial defects and opacification. An obstacle in the treatment of ocular diseases is poor drug delivery and maintenance. In this study, we constructed a Wnt/β-catenin pathway inhibitor, XAV939-loaded liposome (XAV939 NPs), and revealed its anti-inflammatory and antiangiogenic effects. The XAV939 NPs possessed excellent biocompatibility in corneal epithelial cells and mouse corneas. In vitro corneal wound healing assays demonstrated their antiangiogenic effect, and LPS-induced expressions of pro-inflammatory genes of IL-1β, IL-6, and IL-17α were significantly suppressed by XAV939 NPs. In addition, the XAV939 NPs significantly ameliorated alkali-burned corneas with slight corneal opacity, reduced neovascularization, and faster recovery, which were attributed to the decreased gene expressions of angiogenic and inflammatory cytokines. The findings supported the potential of XAV939 NPs in ameliorating corneal wound and suppressing neovascularization, providing evidence for their clinical application in ocular vascular diseases.
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spelling doaj.art-4fe46abec4eb44ccae46432d29e000432022-12-21T21:31:03ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852021-10-01910.3389/fbioe.2021.753879753879Ocular Wnt/β-Catenin Pathway Inhibitor XAV939-Loaded Liposomes for Treating Alkali-Burned Corneal Wound and NeovascularizationYueyang Zhong0Yueyang Zhong1Kai Wang2Kai Wang3Yin Zhang4Yin Zhang5Qichuan Yin6Qichuan Yin7Su Li8Su Li9Jiaming Wang10Xiaobo Zhang11Xiaobo Zhang12Haijie Han13Haijie Han14Ke Yao15Ke Yao16Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaZhejiang Provincial Key Lab of Ophthalmology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaEye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaZhejiang Provincial Key Lab of Ophthalmology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaEye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaZhejiang Provincial Key Lab of Ophthalmology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaEye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaZhejiang Provincial Key Lab of Ophthalmology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaEye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaZhejiang Provincial Key Lab of Ophthalmology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaThe First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, State Key Laboratory of Experimental Hematology, School of Medicine, Zhejiang University, Hangzhou, ChinaEye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaZhejiang Provincial Key Lab of Ophthalmology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaEye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaZhejiang Provincial Key Lab of Ophthalmology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaEye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaZhejiang Provincial Key Lab of Ophthalmology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaCorneal wound involves a series of complex and coordinated physiological processes, leading to persistent epithelial defects and opacification. An obstacle in the treatment of ocular diseases is poor drug delivery and maintenance. In this study, we constructed a Wnt/β-catenin pathway inhibitor, XAV939-loaded liposome (XAV939 NPs), and revealed its anti-inflammatory and antiangiogenic effects. The XAV939 NPs possessed excellent biocompatibility in corneal epithelial cells and mouse corneas. In vitro corneal wound healing assays demonstrated their antiangiogenic effect, and LPS-induced expressions of pro-inflammatory genes of IL-1β, IL-6, and IL-17α were significantly suppressed by XAV939 NPs. In addition, the XAV939 NPs significantly ameliorated alkali-burned corneas with slight corneal opacity, reduced neovascularization, and faster recovery, which were attributed to the decreased gene expressions of angiogenic and inflammatory cytokines. The findings supported the potential of XAV939 NPs in ameliorating corneal wound and suppressing neovascularization, providing evidence for their clinical application in ocular vascular diseases.https://www.frontiersin.org/articles/10.3389/fbioe.2021.753879/fullliposomesWnt/β-catenin pathwayXAV939corneal woundcorneal neovascularization
spellingShingle Yueyang Zhong
Yueyang Zhong
Kai Wang
Kai Wang
Yin Zhang
Yin Zhang
Qichuan Yin
Qichuan Yin
Su Li
Su Li
Jiaming Wang
Xiaobo Zhang
Xiaobo Zhang
Haijie Han
Haijie Han
Ke Yao
Ke Yao
Ocular Wnt/β-Catenin Pathway Inhibitor XAV939-Loaded Liposomes for Treating Alkali-Burned Corneal Wound and Neovascularization
Frontiers in Bioengineering and Biotechnology
liposomes
Wnt/β-catenin pathway
XAV939
corneal wound
corneal neovascularization
title Ocular Wnt/β-Catenin Pathway Inhibitor XAV939-Loaded Liposomes for Treating Alkali-Burned Corneal Wound and Neovascularization
title_full Ocular Wnt/β-Catenin Pathway Inhibitor XAV939-Loaded Liposomes for Treating Alkali-Burned Corneal Wound and Neovascularization
title_fullStr Ocular Wnt/β-Catenin Pathway Inhibitor XAV939-Loaded Liposomes for Treating Alkali-Burned Corneal Wound and Neovascularization
title_full_unstemmed Ocular Wnt/β-Catenin Pathway Inhibitor XAV939-Loaded Liposomes for Treating Alkali-Burned Corneal Wound and Neovascularization
title_short Ocular Wnt/β-Catenin Pathway Inhibitor XAV939-Loaded Liposomes for Treating Alkali-Burned Corneal Wound and Neovascularization
title_sort ocular wnt β catenin pathway inhibitor xav939 loaded liposomes for treating alkali burned corneal wound and neovascularization
topic liposomes
Wnt/β-catenin pathway
XAV939
corneal wound
corneal neovascularization
url https://www.frontiersin.org/articles/10.3389/fbioe.2021.753879/full
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