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Herein, carbon nanodonuts (CNDs) with a donut\u2010shaped structure are synthesized using sodium alginate (SA) and 1,8\u2010diaminooctane (DAO) through a one\u2010step thermal process. The formation of SA\/DAO\u2010CNDs occurs through a crosslinking reaction between SA and DAO, creating amide bonds followed by partial carbonization. In human retinal pigment epithelial\u00a0cells exposed to H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> or lipopolysaccharide, the SA\/DAO\u2010CNDs display a more than fivefold reduction in reactive oxygen species and proinflammatory cytokines, such as IL\u20106 and IL\u20101\u03b2, when compared to carbonized nanomaterials produced exclusively from SA. Furthermore, the CNDs effectively inhibit vascular endothelial growth factor A\u2010165 (VEGF\u2010A<jats:sub>165<\/jats:sub>)\u2010induced cell migration and tube formation in human umbilical vein endothelial cells due to their strong affinity for VEGF\u2010A<jats:sub>165<\/jats:sub>, with a dissociation constant of 2.2 \u00d7 10<jats:sup>\u221214<\/jats:sup>\u00a0<jats:sc>M<\/jats:sc>, over 1600 times stronger than the commercial drug bevacizumab (Avastin). Trypsin digestion coupled with LC\u2010MS\/MS analysis reveals that VEGF\u2010A<jats:sub>165<\/jats:sub> interacts with SA\/DAO\u2010CNDs through its heparin\u2010binding domain, leading to activity loss. The SA\/DAO\u2010CNDs demonstrate excellent biocompatibility and potent anti\u2010angiogenic effects in chicken embryos and rabbit eyes. These findings suggest that SA\/DAO\u2010CNDs hold promise as a therapeutic agent for treating various angiogenesis\u2010related ocular diseases.<\/jats:p>","DOI":"10.1002\/adhm.202302881","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T01:38:26Z","timestamp":1703209106000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Ultrahigh\u2010Efficacy VEGF Neutralization Using Carbonized Nanodonuts: Implications for Intraocular Anti\u2010Angiogenic Therapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Hong\u2010Jyuan","family":"Jian","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Chang Gung University  Taoyuan 33302 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anisha","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Chang Gung University  Taoyuan 33302 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