Ultrahigh-Efficacy VEGF Neutralization Using Carbonized Nanodonuts: Implications for Intraocular Anti-Angiogenic Therapy.

Autor: Jian HJ; Department of Biomedical Engineering, Chang Gung University, Taoyuan, 33302, Taiwan., Anand A; Department of Biomedical Engineering, Chang Gung University, Taoyuan, 33302, Taiwan., Lai JY; Department of Biomedical Engineering, Chang Gung University, Taoyuan, 33302, Taiwan.; Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan, 33305, Taiwan.; Department of Materials Engineering, Ming Chi University of Technology, New Taipei City, 24301, Taiwan.; Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, 33303, Taiwan., Huang CC; Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, 20224, Taiwan.; Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, 20224, Taiwan.; School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan., Ma DH; Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan, 33305, Taiwan.; Department of Chinese Medicine, Chang Gung University, Taoyuan, 33302, Taiwan., Lai CC; Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan, 33305, Taiwan.; College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan.; Department of Ophthalmology, Chang Gung Memorial Hospital, Keelung, 20401, Taiwan., Chang HT; Department of Biomedical Sciences, Chang Gung University, Taoyuan, 33302, Taiwan.; Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, 33302, Taiwan.; Center for Advanced Biomaterials and Technology Innovation, Chang Gung University, Taoyuan, 33302, Taiwan.; Division of Breast Surgery, Department of General Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan, 33305, Taiwan.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2024 Mar; Vol. 13 (7), pp. e2302881. Date of Electronic Publication: 2023 Dec 27.
DOI: 10.1002/adhm.202302881
Abstrakt: Ocular angiogenesis, associated with diseases such as retinopathy of prematurity and diabetic retinopathy, is a leading cause of irreversible vision loss. Herein, carbon nanodonuts (CNDs) with a donut-shaped structure are synthesized using sodium alginate (SA) and 1,8-diaminooctane (DAO) through a one-step thermal process. The formation of SA/DAO-CNDs occurs through a crosslinking reaction between SA and DAO, creating amide bonds followed by partial carbonization. In human retinal pigment epithelial cells exposed to H 2 O 2 or lipopolysaccharide, the SA/DAO-CNDs display a more than fivefold reduction in reactive oxygen species and proinflammatory cytokines, such as IL-6 and IL-1β, when compared to carbonized nanomaterials produced exclusively from SA. Furthermore, the CNDs effectively inhibit vascular endothelial growth factor A-165 (VEGF-A 165 )-induced cell migration and tube formation in human umbilical vein endothelial cells due to their strong affinity for VEGF-A 165 , with a dissociation constant of 2.2 × 10 -14  M, over 1600 times stronger than the commercial drug bevacizumab (Avastin). Trypsin digestion coupled with LC-MS/MS analysis reveals that VEGF-A 165 interacts with SA/DAO-CNDs through its heparin-binding domain, leading to activity loss. The SA/DAO-CNDs demonstrate excellent biocompatibility and potent anti-angiogenic effects in chicken embryos and rabbit eyes. These findings suggest that SA/DAO-CNDs hold promise as a therapeutic agent for treating various angiogenesis-related ocular diseases.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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