Anti-Flt1 peptide - hyaluronate conjugate for the treatment of retinal neovascularization and diabetic retinopathy
Abstract
Anti-angiogenic therapeutics has been investigated extensively for the treatment of retinal and choroidal vascular diseases, and diabetic retinopathy. Anti-Flt1 peptide of GNQWFI is an antagonistic peptide for vascular endothelial growth factor receptor 1 (VEGFR1 or Flt1) inhibiting VEGFR1-mediated endothelial cell migration and tube formation. In this work, anti-Flt1 peptide (GGNQWFI) was chemically conjugated to tetra-n-butyl ammonium modified hyaluronate (HA-TBA) via amide bond formation in dimethyl sulfoxide (DMSO) using benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP). The resulting HA - GGNQWFI conjugate self-assembled to form micelle-like nanoparticles in aqueous solution, as confirmed and characterized by transmission electron microscopy (TEM). According to in vitro biological activity tests, HA - GGNQWFI conjugate exhibited a dose-dependent inhibition effect on the binding of Flt1-Fc to VEGF(165) coated on the well. Furthermore, anti-Flt1 peptide - HA conjugate effectively inhibited retinal choroidal neovascularization (CNV) in laser induced CNV model rats. The retinal vascular permeability and the deformation of retinal vascular structure were also significantly reduced in diabetic retinopathy model rats after treatment with anti-Flt1 peptide - HA conjugate. Pharmacokinetic analysis confirmed the increased mean residence time of anti-Flt1 peptide after conjugation to HA longer than 2 weeks.
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Treatment with anti-Flt1 peptide-HA conjugate significantly reduced retinal vascular permeability and deformation of retinal vascular structures in DR model rats.
“Notably, treatment with the anti-Flt1 peptide-HA conjugate significantly reduced retinal vascular permeability and deformation of retinal vascular structures in DR model rats [203].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [203]
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References 35 · Cited by 77
- Authors
- Oh, E. J., Choi, J.-S., Kim, H., Joo, C.-K., & Hahn, S. K.
- Affiliations
- Pohang University of Science and Technology (KR)
- The Catholic University of Korea Seoul St. Mary's Hospital (KR)
- Corresponding author
- Joo, Choun-Ki
- Hahn, Sei Kwang
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 32
- Issue
- 11
- Pages
- 3115-3123
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2006436822
- Cited by
- 77
- References
- 35
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 3 · 2021: 7 · 2020: 5 · 2019: 6 · 2018: 9 · 2017: 3 · 2016: 6 · 2015: 3 · 2014: 6 · 2013: 1 · 2012: 4
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Open Access System for Information Sharing (Pohang University of Science and Technology) (submittedVersion)
- Funders
- Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea
- MEST (2009-0084578)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- retinal neovascularization, choroidal neovascularization, diabetic retinopathy, anti-angiogenic therapy, peptide-nanoparticle conjugates, laser-induced CNV, retinal vascular permeability, pharmacokinetics, VEGF inhibition
- MeSH terms
- Animals, Diabetic Retinopathy, Hyaluronic Acid, Male, Peptides, Retinal Neovascularization, Rats, Sprague-Dawley, Vascular Endothelial Growth Factor Receptor-1, Rats
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