A Bifunctional Peptide with Penetration Ability for Treating Retinal Angiogenesis via Eye Drops.

IF 4.5 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Molecular Pharmaceutics Pub Date : 2025-02-03 Epub Date: 2025-01-14 DOI:10.1021/acs.molpharmaceut.4c00683
Jing Liao, Lin Zhao, Hongyuan Chen, Chunqian Zhao, Shang Chen, Xiuli Guo, Fengshan Wang, Xiaoxue Liu, Xinke Zhang
{"title":"A Bifunctional Peptide with Penetration Ability for Treating Retinal Angiogenesis via Eye Drops.","authors":"Jing Liao, Lin Zhao, Hongyuan Chen, Chunqian Zhao, Shang Chen, Xiuli Guo, Fengshan Wang, Xiaoxue Liu, Xinke Zhang","doi":"10.1021/acs.molpharmaceut.4c00683","DOIUrl":null,"url":null,"abstract":"<p><p>Numerous diseases, such as diabetic retinopathy and age-related macular degeneration, can lead to retinal neovascularization, which can seriously impair the visual function and potentially result in blindness. The presence of the blood-retina barrier makes it challenging for ocularly administered drugs to penetrate physiological barriers and reach the ocular posterior segments, including the retina and choroid. Herein, we developed an innovative bifunctional peptide, Tat-C-RP7, which exhibits excellent penetration capabilities and antiangiogenic properties aimed at treating retinal neovascularization diseases. RP7 is an NRP-1 targeting peptide that blocks vascular endothelial growth factor receptor-2 (VEGFR-2) signaling and inhibits angiogenesis, while Tat facilitates the delivery of various cargoes across biological barriers, such as the blood-retina barrier. By combining these attributes, Tat-C-RP7 is anticipated to traverse ocular barriers via ocular topical administration and exert its antiangiogenic effects in the ocular posterior segment. Experimental results demonstrated that Tat-C-RP7 significantly inhibited the proliferation and migration of rat retinal microvascular endothelial cells and effectively reduced tubule formation <i>in vitro</i>. Its antiangiogenic activity was confirmed in zebrafish. The outstanding penetrative capabilities of FITC-labeled Tat-C-RP7 have been validated through cell uptake assays, <i>in vitro</i> cell barrier models, <i>ex-vivo</i> ocular tissues, and <i>in vivo</i> studies. Besides, the half-life of Tat-C-RP7 was longer than that of RP7. In an oxygen-induced retinopathy model, Tat-C-RP7 was shown to reduce the area of angiogenesis following ocular administration. Additionally, it produced no irritating effects on the eyes of rabbits. Overall, Tat-C-RP7 demonstrates excellent ocular penetrability and antiangiogenic effects and represents a promising therapeutic option for treating retinal neovascularization diseases.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"708-720"},"PeriodicalIF":4.5000,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acs.molpharmaceut.4c00683","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/14 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

Abstract

Numerous diseases, such as diabetic retinopathy and age-related macular degeneration, can lead to retinal neovascularization, which can seriously impair the visual function and potentially result in blindness. The presence of the blood-retina barrier makes it challenging for ocularly administered drugs to penetrate physiological barriers and reach the ocular posterior segments, including the retina and choroid. Herein, we developed an innovative bifunctional peptide, Tat-C-RP7, which exhibits excellent penetration capabilities and antiangiogenic properties aimed at treating retinal neovascularization diseases. RP7 is an NRP-1 targeting peptide that blocks vascular endothelial growth factor receptor-2 (VEGFR-2) signaling and inhibits angiogenesis, while Tat facilitates the delivery of various cargoes across biological barriers, such as the blood-retina barrier. By combining these attributes, Tat-C-RP7 is anticipated to traverse ocular barriers via ocular topical administration and exert its antiangiogenic effects in the ocular posterior segment. Experimental results demonstrated that Tat-C-RP7 significantly inhibited the proliferation and migration of rat retinal microvascular endothelial cells and effectively reduced tubule formation in vitro. Its antiangiogenic activity was confirmed in zebrafish. The outstanding penetrative capabilities of FITC-labeled Tat-C-RP7 have been validated through cell uptake assays, in vitro cell barrier models, ex-vivo ocular tissues, and in vivo studies. Besides, the half-life of Tat-C-RP7 was longer than that of RP7. In an oxygen-induced retinopathy model, Tat-C-RP7 was shown to reduce the area of angiogenesis following ocular administration. Additionally, it produced no irritating effects on the eyes of rabbits. Overall, Tat-C-RP7 demonstrates excellent ocular penetrability and antiangiogenic effects and represents a promising therapeutic option for treating retinal neovascularization diseases.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
一种具有穿透能力的双功能肽滴眼液治疗视网膜血管生成。
许多疾病,如糖尿病视网膜病变和年龄相关性黄斑变性,可导致视网膜新生血管,这可能严重损害视觉功能,并可能导致失明。血液-视网膜屏障的存在使得眼部给药药物很难穿透生理屏障到达眼后段,包括视网膜和脉络膜。在此,我们开发了一种创新的双功能肽Tat-C-RP7,它具有优异的渗透能力和抗血管生成特性,旨在治疗视网膜新生血管疾病。RP7是一种NRP-1靶向肽,可阻断血管内皮生长因子受体-2 (VEGFR-2)信号传导并抑制血管生成,而RP7可促进各种物质跨越生物屏障(如血液-视网膜屏障)的输送。结合这些特性,Tat-C-RP7有望通过眼部局部给药穿越眼屏障,并在眼后段发挥其抗血管生成作用。实验结果表明,Tat-C-RP7在体外可显著抑制大鼠视网膜微血管内皮细胞的增殖和迁移,有效减少小管的形成。其抗血管生成活性在斑马鱼中得到证实。fitc标记的Tat-C-RP7的卓越穿透能力已通过细胞摄取试验、体外细胞屏障模型、离体眼组织和体内研究得到验证。此外,Tat-C-RP7的半衰期比RP7长。在氧诱导视网膜病变模型中,Tat-C-RP7可减少眼部给药后血管生成的面积。此外,它对兔子的眼睛没有刺激作用。总的来说,Tat-C-RP7具有良好的眼穿透性和抗血管生成作用,是治疗视网膜新生血管疾病的一种有希望的治疗选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
相关文献
Logic Gates and Boolean Algebra
IF 0 SK International Journal of Multidisciplinary Research HubPub Date : 2014-11-01 DOI: 10.61165/sk.publisher.v1i1.2
Kalyani M. Raval
Boolean Algebra and Logic Gates
IF 0 International Journal of Mathematics Trends and TechnologyPub Date : 2019-03-25 DOI: 10.14445/22315373/IJMTT-V65I3P522
Subhrajit Sarma, Rama Kanta Bhuyan
Boolean Algebra and Logic Gates
IF 0 Electronic Digital System FundamentalsPub Date : 2020-12-14 DOI: 10.1201/9781003151395-3
D. Patrick, Stephen W. Fardo, V. Chandra
来源期刊
Molecular Pharmaceutics
Molecular Pharmaceutics 医学-药学
CiteScore
8.00
自引率
6.10%
发文量
391
审稿时长
2 months
期刊介绍: Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development. Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.
期刊最新文献
Development of a Novel 18F-Labeled Radioligand for Imaging Phosphodiesterase 7 with Positron Emission Tomography. Optimizing Andrographolide from Sambiloto Leaves (Andrographis paniculata) Using Cyclodextrin Metal-Organic Frameworks for Targeted Pulmonary Delivery via a Metered Dose Inhaler: A Proof-Of-Concept Study. 68Ga-Labeled Glycopeptides as Effective Tools for Liver Function Imaging. Large-Scale Compartmental Model-Based Study of Preclinical Pharmacokinetic Data and Its Impact on Compound Triaging in Drug Discovery. Oral DNA Vaccine Utilizing the Yeast Cell Wall for Dectin-1 Receptor-Mediated Enhancement of Mucosal Immunity.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1