Disrupting the Oxidative Stress-Inflammation-Corneal Neovascularization Cycle with Ultrasmall Nanoparticles

  • Adv Mater. 2026 Apr 24:e73114. doi: 10.1002/adma.73114.
Yue Wu  1  2  3 ,  Nan Zhao  1  2  3 ,  Xue Liu  1  4 ,  Zhongxing Chen  1  2  3 ,  Xiaomin Huang  1  2  3 ,  Hongxian Pan  1  2  3 ,  Mengmei Zhu  4 ,  Zheyu Li  5 ,  Xinyu Jiang  5 ,  Xueyu Fu  1  2  3 ,  Haochen Liu  1  2  3 ,  Weiping Wang  6 ,  Xin Chen  1  2  3 ,  Manli Deng  1  2  3 ,  Jihong Wu  1  2  3 ,  Yi Shao  7 ,  Wei Tao  8 ,  Mei Yang  1  2  3 ,  Xingtao Zhou  1  2  3 ,  Jinhai Huang  1  2  3
Affiliations
  • 1. Eye Institute and Department of Ophthalmology, NHC Key Laboratory of Myopia and Related Eye Diseases, Eye & ENT Hospital, Fudan University, Shanghai, China.
  • 2. Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China.
  • 3. Shanghai Research Center of Ophthalmology and Optometry, Shanghai, China.
  • 4. School of Health Sciences and Engineering, University of Shanghai for Science and Technology, Shanghai, China.
  • 5. School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 6. State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong; Department of Pharmacology & Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong; Laboratory of Molecular Engineering and Nanomedicine, Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong, China.
  • 7. Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai, China.
  • 8. Center For Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
PMID: 42032871 DOI: 10.1002/adma.73114
Abstract

Corneal neovascularization (CoNV) is a primary contributor to corneal scarring and vision impairment. During its initiation and progression, inflammatory reactions and oxidative stress synergistically trigger a pathological vicious cycle of oxidative stress, inflammation, and angiogenesis, posing a severe therapeutic challenge. In this study, a noninvasive transepithelial therapeutic strategy using ultrasmall polydopamine nanoparticles (UPDA NPs) with triple effects is developed. Their unique small size, approximately 3 nm, greatly enhances their radical-scavenging capability and facilitates superior transepithelial delivery. Extensive research demonstrated that the obtained UPDA NPs possess excellent anti-inflammatory, antioxidant, and anti-angiogenic properties. By scavenging Reactive Oxygen Species (ROS), activating the nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant pathway, and suppressing multiple proangiogenic signaling cascades, they can disrupt the pathological cycle of inflammation, oxidative stress, and neovascularization at molecular, cellular, and animal levels. In an alkali-burned mouse model, UPDA NPs notably reduce CoNV area and length, accelerate corneal repair, and exhibit no local or systemic toxicity, providing a new nanomedicine with translational potential for precise treatment of CoNV.

Keywords
corneal neovascularization; oxidative stress; polydopamine; transepithelial therapy; ultrasmall nanoparticles.
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