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Development of mucoadhesive cationic polypeptide micelles for sustained cabozantinib release and inhibition of corneal neovascularization
Abstract
Corneal neovascularization (CNV) is one of the leading risk factors for vision loss. Anti-angiogenic drugs can theoretically be extended to the treatment of CNV. However, the application of these drugs is often hindered by traditional administration methods, e.g., eye drops, which is ascribed to the unique structure of the cornea and tear film. In this study, cationic polypeptide nanoparticles with mucoadhesive ability that carry lipophilic cabozantinib (a tyrosine kinase inhibitor), called Cabo-NPs, were developed for sustained cabozantinib release and inhibition of CNV. The polypeptides were synthesized via N-carboxyanhydride ring-opening polymerization and could self-assemble into micelles with cabozantinib in aqueous solution. The Cabo-NPs possessed good biocompatibility both in corneal epithelial cells and mouse corneas. More importantly, in vitro angiogenesis assays demonstrated the strong inhibitory effect of Cabo-NPs on cell migration and tube formation. Furthermore, the Cabo-NPs exerted superior anti-angiogenic effects with remarkable reductions in the neovascular area, which were as effective as the clinical dexamethasone but without apparent side effects. The therapeutic mechanism of the Cabo-NPs is closely related to the significant decrease in proangiogenic and proinflammatory factors, suppressing neovascularization and inflammation. Overall, cationic Cabo-NPs offer a new prospect for safe and effective CNV treatment via enhancing the bioavailability of lipophilic cabozantinib.
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In vitro angiogenesis assays certified Cabo-NPs potently suppressed both cell migration and tube formation.
“In vitro angiogenesis assays certified Cabo-NPs potently suppressed both cell migration and tube formation.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [168]
Cabo-NPs showed remarkable reductions in neovascular area without apparent side effects.
“Cabo-NPs showed remarkable reductions in neovascular area without apparent side effects [168].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [168]
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Metadata
- Authors
- Han, H., Yin, Q., Tang, X., Yu, X., Gao, Q., Tang, Y., Grzybowski, A., Yao, K., Ji, J., & Shentu, X.
- Affiliations
- Second Affiliated Hospital of Zhejiang University (CN)
- Ministry of Education of the People's Republic of China (CN)
- Department of Neurology
- University of Warmia and Mazury in Olsztyn (PL)
- Corresponding author
- Ji, Jian
- Shentu, Xingchao
- Venue
- Journal of Materials Chemistry B
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2020
- Volume
- 8
- Issue
- 23
- Pages
- 5143-5154
- ISSN
- 2050-750X (ISSN-L)
- 2050-7518
- OpenAlex
- W3023718056
- Cited by
- 53
- References
- 45
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 7 · 2023: 8 · 2022: 6 · 2021: 11 · 2020: 2
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Materials Chemistry B (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Zhejiang Province (LQ20E030011, LY17H090004)
- National Natural Science Foundation of China (81670834, 81800807, 81800869, 81970781)
- Fundamental Research Funds for the Central Universities (2019FZA7005)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Health Sciences › Medicine › Ophthalmology › Corneal Surgery and Treatments
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- corneal neovascularization, cabozantinib, mucoadhesive nanoparticles, sustained drug release, N-carboxyanhydride ring-opening polymerization, angiogenesis inhibition, keratitis, tyrosine kinase inhibitors, ocular drug delivery
- MeSH terms
- Adhesives, Anilides, Animals, Biocompatible Materials, Cations, Cells, Cultured, Humans, Micelles, Particle Size, Peptides, Pyridines, Sodium Hydroxide, Surface Properties, Corneal Neovascularization, Angiogenesis Inhibitors, Cell Proliferation, Mice, Drug Liberation
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