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<p>Corneal neovascularization (CNV) is one of the leading causes of corneal blindness, affecting millions of people worldwide. Anti-vascular endothelial growth factor agents, such as Bevacizumab (Beva), offer high specificity and low side effects. However, their limited ability to penetrate the corneal barrier necessitates invasive administration, significantly restricting their clinical application. Herein, we engineered (Beva&amp;C₂G₂R₉)@Zn nanoparticles formed by co-assembling Beva, C₂G₂R₉ peptide and Zn<sup>2+</sup>, which decrease in size over time, as an efficient strategy for noninvasive Beva delivery across the corneal barrier to treat CNV. By combining various technologies (DLS, TEM, XPS, FTIR, and computer simulation), we discovered that the coordination between Beva and Zn<sup>2+</sup> drives the nanoparticle formation, while the C₂G₂R₉ peptide facilitates its size evolution. Compared to size-stable nanoparticles of Beva@Zn and (Beva&amp;R₉)@Zn, (Beva&amp;C₂G₂R₉)@Zn nanoparticles exhibit rapid cellular internalization, efficient lysosomal escape, and effective corneal barrier penetration, leading to efficiently inhibit HUVEC cell migration and tube formation. Importantly, in a rat alkali-burned CNV model, (Beva&amp;C₂G₂R₉)@Zn nanoparticles exhibited superior efficacy in inhibiting corneal neovascularization compared to size-stable nanoparticles, with the lowest inflammation index. The results of this study highlight the importance of controlling the size of nanoparticles to enable non-invasive delivery of macromolecular drugs across the corneal biological barrier, offering new insights for the design of future nanoparticle-based drug delivery systems.</p> Graphical Abstract <p></p>

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Size-shrinking nanoparticles with high drug-protein payload for efficient, non-invasive treatment of corneal neovascularization

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月10日

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  • Xiaoling Xie,
  • Zhenyang Xiang,
  • Ruhui Yang,
  • Xuanlu Wu,
  • Jinyu Guo,
  • Ruolin Fang,
  • Xingjie Zan,
  • Wenjuan Huang,
  • Yuhua Tong

摘要

Corneal neovascularization (CNV) is one of the leading causes of corneal blindness, affecting millions of people worldwide. Anti-vascular endothelial growth factor agents, such as Bevacizumab (Beva), offer high specificity and low side effects. However, their limited ability to penetrate the corneal barrier necessitates invasive administration, significantly restricting their clinical application. Herein, we engineered (Beva&C₂G₂R₉)@Zn nanoparticles formed by co-assembling Beva, C₂G₂R₉ peptide and Zn2+, which decrease in size over time, as an efficient strategy for noninvasive Beva delivery across the corneal barrier to treat CNV. By combining various technologies (DLS, TEM, XPS, FTIR, and computer simulation), we discovered that the coordination between Beva and Zn2+ drives the nanoparticle formation, while the C₂G₂R₉ peptide facilitates its size evolution. Compared to size-stable nanoparticles of Beva@Zn and (Beva&R₉)@Zn, (Beva&C₂G₂R₉)@Zn nanoparticles exhibit rapid cellular internalization, efficient lysosomal escape, and effective corneal barrier penetration, leading to efficiently inhibit HUVEC cell migration and tube formation. Importantly, in a rat alkali-burned CNV model, (Beva&C₂G₂R₉)@Zn nanoparticles exhibited superior efficacy in inhibiting corneal neovascularization compared to size-stable nanoparticles, with the lowest inflammation index. The results of this study highlight the importance of controlling the size of nanoparticles to enable non-invasive delivery of macromolecular drugs across the corneal biological barrier, offering new insights for the design of future nanoparticle-based drug delivery systems.

Graphical Abstract