Vascular Endothelial Growth Factor Receptor 1 Targeting Fusion Polypeptides with Stimuli-Responsiveness for Anti-angiogenesis
- Authors
- Kang, Min Jeong; Roh, Kug-Hwan; Lee, Jae Sang; Lee, Jae Hee; Park, SaeGwang; Lim, Dong Woo
- Issue Date
- Jun-2023
- Publisher
- American Chemical Society
- Keywords
- vascular endothelial growth factor receptor 1 targetingpeptide; elastin-based polypeptides; stimuli-responsiveness; anti-angiogenesis; neovascular diseases
- Citation
- ACS Applied Materials & Interfaces, pp.1 - 14
- Indexed
- SCIE
SCOPUS
- Journal Title
- ACS Applied Materials & Interfaces
- Start Page
- 1
- End Page
- 14
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/187446
- DOI
- 10.1021/acsami.3c03989
- ISSN
- 1944-8244
- 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.
- Files in This Item
-
Go to Link
- Appears in
Collections - ETC > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/187446)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.