.png){kind=icon}
.png){kind=icon}
Return
Ultrahigh-Efficacy VEGF Neutralization Using Carbonized Nanodonuts: Implications for Intraocular Anti-Angiogenic Therapy
.png){kind=icon}
PRE
AI
DOI：10.1002/adhm.202302881.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
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-1 beta, 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 x 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.image
Keywords:
ENDOTHELIAL GROWTH-FACTOR
HEPARIN-BINDING DOMAIN
MACULAR DEGENERATION
RED FLUORESCENCE
QUANTUM DOTS
NANOTUBES
MECHANISM
Journal
IF:
9.6
Papers:
7.5K
Citations:
4.4W
Organization
View more organizations