Vascular Endothelial Growth Factor Receptor 1 Targeting Fusion Polypeptides with Stimuli-Responsiveness for Anti-angiogenesis
- Title
- Vascular Endothelial Growth Factor Receptor 1 Targeting Fusion Polypeptides with Stimuli-Responsiveness for Anti-angiogenesis
- Author
- 임동우
- Keywords
- vascular endothelial growth factor receptor 1 targeting peptide; lastin-based polypeptides; stimuli-responsiveness; anti-angiogenesis; neovascular diseases
- Issue Date
- 2023-06-29
- Publisher
- AMER CHEMICAL SOC
- Citation
- ACS APPLIED MATERIALS & INTERFACES, v. 15, NO 27, Page. 32201-32214
- Abstract
- Genetically engineered fusion polypeptideshave beeninvestigatedto introduce unique bio-functionality and improve some therapeuticactivity for anti-angiogenesis. We report herein that stimuli-responsive,vascular endothelial growth factor receptor 1 (VEGFR1) targeting fusionpolypeptides composed of a VEGFR1 (fms-like tyrosine kinase-1 (Flt1))antagonist, an anti-Flt1 peptide, and a thermally responsive elastin-basedpolypeptide (EBP) were rationally designed at the genetic level, biosynthesized,and purified by inverse transition cycling to develop potential anti-angiogenicfusion polypeptides to treat neovascular diseases. A series of hydrophilicEBPs with different block lengths were fused with an anti-Flt1 peptide,forming anti-Flt1-EBPs, and the effect of EBP block length on theirphysicochemical properties was examined. While the anti-Flt1 peptidedecreased phase-transition temperatures of anti-Flt1-EBPs, comparedwith EBP blocks, anti-Flt1-EBPs were soluble under physiological conditions.The anti-Flt1-EBPs dose dependently inhibited the binding of VEGFR1against vascular endothelial growth factor (VEGF) as well as tube-likenetwork formation of human umbilical vein endothelial cells underVEGF-triggered angiogenesis in vitro because of the specific bindingbetween anti-Flt1-EBPs and VEGFR1. Furthermore, the anti-Flt1-EBPssuppressed laser-induced choroidal neovascularization in a wet age-relatedmacular degeneration mouse model in vivo. Our results indicate thatanti-Flt1-EBPs as VEGFR1-targeting fusion polypeptides have greatpotential for efficacious anti-angiogenesis to treat retinal-, corneal-,and choroidal neovascularization.
- URI
- https://information.hanyang.ac.kr/#/eds/detail?an=edselc.2-52.0-85164625617&dbId=edselchttps://repository.hanyang.ac.kr/handle/20.500.11754/190379
- ISSN
- 1944-8252; 1944-8244
- DOI
- 10.1021/acsami.3c03989
- Appears in Collections:
- COLLEGE OF ENGINEERING SCIENCES[E](공학대학) > BIONANO ENGINEERING(생명나노공학과) > Articles
- Files in This Item:
- 2023.6_임동우_Vascular Endothelial Growth Factor Receptor 1 Targeting FusionPolypeptides with Stimuli-Responsiveness for Anti-angiogenesis.pdfDownload
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