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

• Published in: Advanced healthcare materials 2024-03, Vol.13 (7), p.e2302881-n/a
• Main Authors: Jian, Hong‐Jyuan, Anand, Anisha, Lai, Jui‐Yang, Huang, Chih‐Ching, Ma, David Hui‐Kang, Lai, Chi‐Chun, Chang, Huan‐Tsung
• Format: Article
• Language: English
• Subjects: Alginic acid; Angiogenesis; Bevacizumab; Biocompatibility; Cell migration; Crosslinking; Diabetes mellitus; Diabetic retinopathy; Embryos; Endothelial cells; Epithelium; Eye diseases; Growth factors; Heparin; Hydrogen peroxide; Inflammation; Lipopolysaccharides; Nanomaterials; Nanotechnology; Pharmacology; Reactive oxygen species; Retinal pigment epithelium; Retinopathy; Sodium alginate; Trypsin; Umbilical vein; Vascular endothelial growth factor
• ISSN: 2192-2640; 2192-2659; 2192-2659
• DOI: 10.1002/adhm.202302881

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 H2O2 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‐A165)‐induced cell migration and tube formation in human umbilical vein endothelial cells due to their strong affinity for VEGF‐A165, 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‐A165 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. Carbon nanodonuts (CNDs) synthesized from sodium alginate and 1,8‐diaminooctane exhibit exceptional biocompatibility, stability, and multifaceted therapeutic benefits, such as antioxidant, anti‐inflammatory, and anti‐angiogenic properties. Remarkably, these CNDs outperform the commercially available drug, bevacizumab, in effectively trapping vascular endothelial growth factor (VEGF), and stand out as a groundbreaking treatment for angiogenesis‐related ocular diseases, surpassing current anti‐VEGF therapies.