{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:17:50Z","timestamp":1788153470081,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: Pathological angiogenesis and stromal fibrosis after ocular chemical injury are primary drivers of corneal opacification and permanent vision loss. Topical administration of anti-VEGFA antibody is hampered by rapid tear clearance and poor penetration across the corneal epithelial barrier, resulting in insufficient intraocular drug accumulation and suboptimal therapeutic efficacy. Although intraocular injection elevates local drug concentration, this invasive procedure carries risks of complications and is not suitable for long-term repeated treatment. This study constructed red cabbage-derived exosome-like nanovesicles (Rabexo) to load an anti-VEGFA antibody, formulated into PVA\/HA hydrogel, aiming to develop a topical sustained-release ocular delivery system for alleviating corneal angiogenic and fibrotic lesions. Methods: Rabexo was isolated and physicochemically characterized. Anti-VEGFA antibody was encapsulated into Rabexo via electroporation to prepare aV-Rabexo, which was further incorporated into commercial PVA\/HA hydrogel. Cellular uptake, anti-angiogenic functions were verified in vitro, and therapeutic efficacy was evaluated in a mouse corneal alkali burn model via ophthalmic topical administration. Results: The prepared Rabexo showed uniform size and favorable colloidal stability with 40.3% antibody encapsulation efficiency. aV-Rabexo exhibited stronger in vitro anti-migration, anti-proliferation and anti-tube formation effects than free antibody. In vivo, aV-Rabexo-Gel substantially suppressed corneal neovascular area and length, restored stromal collagen arrangement, and downregulated CD31, VEGFA and \u03b1-SMA expression at day 14 post-injury, with statistically significant differences compared with the free antibody gel. Conclusions: This plant-derived nanocarrier hydrogel system realizes synergistic therapeutic effects via nanocarrier delivery, antibody neutralization and prolonged ocular retention. With advantages of easy production and low immunogenicity, it provides a promising non-surgical strategy for treating ocular surface pathological angiogenesis and fibrosis.<\/jats:p>","DOI":"10.3390\/molecules31173026","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:24:03Z","timestamp":1788150243000},"page":"3026","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Delivery of Anti-VEGFA Antibody by Plant-Derived Exosome-like Nanovesicles Alleviates Corneal Angiogenesis and Fibrosis via Topical Ocular Administration"],"prefix":"10.3390","volume":"31","author":[{"given":"Xuan","family":"Chen","sequence":"first","affiliation":[{"name":"School of Medicine, Tongji University, Shanghai 200092, China"},{"name":"Department of Ophthalmology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9157-2375","authenticated-orcid":false,"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine, Tongji University, Shanghai 200092, China"},{"name":"Department of Ophthalmology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Ping","family":"Cui","sequence":"additional","affiliation":[{"name":"School of Medicine, Tongji University, Shanghai 200092, China"},{"name":"Department of Ophthalmology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/00055735-200108000-00002","article-title":"Corneal Neovascularization","volume":"12","author":"Chang","year":"2001","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2401710","DOI":"10.1002\/advs.202401710","article-title":"Genome Editing VEGFA Prevents Corneal Neovascularization In Vivo","volume":"11","author":"Zeng","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"108272","DOI":"10.1016\/j.exer.2020.108272","article-title":"Corneal Myofibroblasts and Fibrosis","volume":"201","author":"Wilson","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1167\/iovs.66.1.21","article-title":"Recombinant Thrombomodulin Domain 1 Modulates Macrophage Polarization and Enhances Healing in Corneal Alkali Burns","volume":"66","author":"Chang","year":"2025","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jtos.2012.01.005","article-title":"Corneal Neovascularization and the Utility of Topical VEGF Inhibition: Ranibizumab (Lucentis) vs Bevacizumab (Avastin)","volume":"10","author":"Stevenson","year":"2012","journal-title":"Ocul. Surf."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"112274","DOI":"10.1016\/j.msec.2021.112274","article-title":"Inhibiting Corneal Neovascularization by Sustainably Releasing Anti-VEGF and Anti-Inflammation Drugs from Silica-Thermogel Nanohybrids","volume":"128","author":"Lyu","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e202500366","DOI":"10.1002\/cmdc.202500366","article-title":"Recent Progress on Topical Drug Therapy for Corneal Neovascularization","volume":"20","author":"Huang","year":"2025","journal-title":"ChemMedChem"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S354","DOI":"10.4103\/IJO.IJO_3043_23","article-title":"Management of Corneal Neovascularization: Current and Emerging Therapeutic Approaches","volume":"72","author":"Wu","year":"2024","journal-title":"Indian J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jtos.2023.09.008","article-title":"Intrastromal versus Subconjunctival Injection of Mesenchymal Stem\/Stromal Cells for Promoting Corneal Repair","volume":"30","author":"Soleimani","year":"2023","journal-title":"Ocul. Surf."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"871","DOI":"10.18240\/ijo.2023.06.06","article-title":"Subconjunctival Conbercept for the Treatment of Corneal Neovascularization","volume":"16","author":"Sun","year":"2023","journal-title":"Int. J. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s10787-022-01115-7","article-title":"Exosome Engineering in Cell Therapy and Drug Delivery","volume":"31","author":"Sadeghi","year":"2023","journal-title":"Inflammopharmacology"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Serrano, D.R., Juste, F., Anaya, B.J., Ramirez, B.I., S\u00e1nchez-Guirales, S.A., Quispillo, J.M., Hernandez, E.M., Simon, J.A., Trallero, J.M., and Serrano, C. (2025). Exosome-Based Drug Delivery: A Next-Generation Platform for Cancer, Infection, Neurological and Immunological Diseases, Gene Therapy and Regenerative Medicine. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17101336"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1038\/s41551-021-00764-3","article-title":"Reduction of Choroidal Neovascularization via Cleavable VEGF Antibodies Conjugated to Exosomes Derived from Regulatory T Cells","volume":"5","author":"Tian","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"eabj9617","DOI":"10.1126\/sciadv.abj9617","article-title":"miR-204\u2013Containing Exosomes Ameliorate GVHD-Associated Dry Eye Disease","volume":"8","author":"Zhou","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"114899","DOI":"10.1016\/j.addr.2023.114899","article-title":"Advances in Development of Exosomes for Ophthalmic Therapeutics","volume":"199","author":"Tian","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9636897241297623","DOI":"10.1177\/09636897241297623","article-title":"Current Development of Mesenchymal Stem Cell-Derived Extracellular Vesicles","volume":"34","author":"Zheng","year":"2025","journal-title":"Cell Transpl."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1080\/17435889.2026.2683537","article-title":"Overcoming the Barriers to the Scaled-up Production of Therapeutic Bacterial Extracellular Vesicles","volume":"21","author":"Castiglione","year":"2026","journal-title":"Nanomedicine"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tinnirello, V., Rabienezhad Ganji, N., De Marcos Lousa, C., Alessandro, R., and Raimondo, S. (2023). Exploiting the Opportunity to Use Plant-Derived Nanoparticles as Delivery Vehicles. Plants, 12.","DOI":"10.3390\/plants12061207"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s12951-025-03138-y","article-title":"Lemon-Derived Nanoparticle-Functionalized Hydrogels Regulate Macrophage Reprogramming to Promote Diabetic Wound Healing","volume":"23","author":"Jin","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1021\/acsptsci.5c00363","article-title":"Plant-Derived Exosome-Coated Niosome Oxygen Nanobubbles for the Mitigation of Ocular Ischemia","volume":"8","author":"Bushra","year":"2025","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1039\/C7TB03207B","article-title":"Advances in Plant-Derived Edible Nanoparticle-Based Lipid Nano-Drug Delivery Systems as Therapeutic Nanomedicines","volume":"6","author":"Yang","year":"2018","journal-title":"J. Mater. Chem. B"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"101810","DOI":"10.1016\/j.mtbio.2025.101810","article-title":"A Novel Hydrogel Loaded with Plant Exosomes and Stem Cell Exosomes as a New Strategy for Treating Diabetic Wounds","volume":"32","author":"Weng","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5643","DOI":"10.7150\/thno.97139","article-title":"Engineered Plant-Derived Extracellular Vesicles for Targeted Regulation and Treatment of Colitis-Associated Inflammation","volume":"14","author":"Kang","year":"2024","journal-title":"Theranostics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2400640","DOI":"10.1002\/mabi.202400640","article-title":"Coriander-Derived Exosome-Like Nanovesicles Laden Hydrogel with Antioxidant Property Accelerates Wound Healing","volume":"25","author":"Wang","year":"2025","journal-title":"Macromol. Biosci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sabin, O., Pop, R.M., Boc\u0219an, I.C., Chedea, V.S., Ranga, F., Grozav, A., Levai, A.-M., and Buzoianu, A.D. (2024). The Anti-Inflammatory, Analgesic, and Antioxidant Effects of Polyphenols from Brassica Oleracea Var. Capitata Extract on Induced Inflammation in Rodents. Molecules, 29.","DOI":"10.3390\/molecules29153448"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1007\/s10068-025-01904-0","article-title":"Red Cabbage Exosome-like Nanoparticles Inhibited LPS-Induced Inflammation and Oxidative Stress in RAW264.7 Cells","volume":"34","author":"Cao","year":"2025","journal-title":"Food Sci. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7","DOI":"10.2174\/1566523219666181213120634","article-title":"Gene-Based Therapeutic Tools in the Treatment of Cornea Disease","volume":"19","author":"Lu","year":"2019","journal-title":"Curr. Gene Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4598","DOI":"10.7150\/thno.97096","article-title":"Exosome-like Nanoparticles Derived from Fruits, Vegetables, and Herbs: Innovative Strategies of Therapeutic and Drug Delivery","volume":"14","author":"Zhao","year":"2024","journal-title":"Theranostics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"116543","DOI":"10.1016\/j.biopha.2024.116543","article-title":"Research Status and Challenges of Plant-Derived Exosome-like Nanoparticles","volume":"174","author":"Bai","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12283","DOI":"10.1002\/jev2.12283","article-title":"Plant-derived Extracellular Vesicles: Recent Advancements and Current Challenges on Their Use for Biomedical Applications","volume":"11","author":"Lian","year":"2022","journal-title":"J. Extracell. Vesicle"},{"key":"ref_31","first-page":"4321","article-title":"Isolation of Cabbage Exosome-like Nanovesicles and Investigation of Their Biological Activities in Human Cells","volume":"6","author":"You","year":"2021","journal-title":"Bioact. Mater."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.34133\/research.1019","article-title":"Cabbage Exosome-Like Nanoparticles Encapsulating Small Noncoding tsRNA Prevent Postinjury Arterial Restenosis","volume":"8","author":"Liu","year":"2025","journal-title":"Research"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"143923","DOI":"10.1016\/j.ijbiomac.2025.143923","article-title":"PVA\/HA@BT Hydrogel with Antioxidant and Antibacterial Abilities for Accelerating Diabetic Wound Healing","volume":"311","author":"Li","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"14982","DOI":"10.1039\/D5TB01575H","article-title":"Hydrogel-Based Ocular Drug Delivery Systems","volume":"13","author":"Sabbagh","year":"2025","journal-title":"J. Mater. Chem. B"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zhu, W., Xia, M., He, Y., Huang, Q., Liao, Z., Wang, X., Zhou, X., and Duan, X. (2026). Hydrogels as Promising Carriers for Ophthalmic Disease Treatment: A Comprehensive Review. Gels, 12.","DOI":"10.3390\/gels12020105"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1002\/jcb.30344","article-title":"Molecular Mechanism of VEGF and Its Role in Pathological Angiogenesis","volume":"123","author":"Ahmad","year":"2022","journal-title":"J. Cell. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1186\/s12967-025-07102-0","article-title":"Transforming Corneal Alkali Burn Treatment: Unveiling Mechanisms and Pioneering Therapies from Bench to Bedside","volume":"23","author":"Xie","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.freeradbiomed.2025.09.012","article-title":"Targeting ER Stress\/ROS-Driven VEGF Signaling Axis: AdipoRon as a Multifunctional Therapeutic Agent for Alkali Burn-Induced Corneal Neovascularization","volume":"241","author":"Wang","year":"2025","journal-title":"Free Radic. Biol. Med."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/17\/3026\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:26:17Z","timestamp":1788150377000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/17\/3026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":38,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["molecules31173026"],"URL":"https:\/\/doi.org\/10.3390\/molecules31173026","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]}}}