Effective treatment of ocular neovascular diseases hinges on safe and efficient drug delivery. However, the current standard therapy—intraocular injection of anti-VEGF antibodies—is invasive and often leads to poor patient compliance, as well as risks of infection, hemorrhage, and other complications. Thus, there is an urgent need for noninvasive therapeutic strategies, representing a critical unmet challenge in ophthalmology.
A research team led by Jie Zhou, Shuang Lin, and Biting Zhou has recently reported a novel dithiolane-based antibody eye drop formulation, offering a promising noninvasive approach for treating corneal neovascularization. The study identified an anti-VEGF single-domain antibody (sdVE01) that is one-third the size of the clinically used ranibizumab, yet retains comparable anti-angiogenic activity to ranibizumab’s heavy-chain region (VHHL), making it more suitable for crossing ocular barriers. To further enhance ocular surface penetration, the team designed four dithiolane molecules (DMs) to construct stable antibody nanoformulations. These DM-antibody complexes enhance hydrophobicity and tissue permeability through covalent modification, allowing for effective delivery into both the anterior and posterior segments of the eye following topical administration. In animal models, the eye drops significantly suppressed alkali burn-induced corneal neovascularization, achieving therapeutic efficacy on par with subconjunctival injection, without observable toxicity.
This breakthrough offers an innovative solution for transcorneal delivery of large-molecule biologics and paves the way for clinical translation of noninvasive ocular therapies.
The study was accepted on November 17, 2025, and published online in Nano Research (DOI: 10.26599/NR.2025.94907904).
"In this study, we developed a dithiolane-based sdVE01 antibody nanodrop system, achieving enhanced corneal penetration and sustained anti-angiogenic effects through rational carrier design," said Xiaole Chen, corresponding author and professor at the School of Pharmacy, Fujian Medical University. "This platform not only holds promise for corneal neovascularization but also opens new avenues for macromolecular therapeutics in other ocular diseases." Co-corresponding authors Nanwen Zhang and Juhua Yang added, "sdVE01 demonstrates excellent stability and biocompatibility, and when combined with simple eyedrop administration, presents strong potential for clinical application."
This work was supported by the National Natural Science Foundation of China (Nos.22304027, 81570807), the Natural Science Foundation of Fujian Province (Nos. 2022J01208), and the Joint Funds for the Innovation of Science and Technology, Fujian Province (Nos. 2024Y9109, 2024Y9107, 2024Y9103), and the Startup Fund for Scientific Research, Fujian Medical University (Nos.XRCZX2021015), the Scientific Research Foundation of State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory (Nos.2023XAKJ0101018).
About Nano Research
Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 7,000 articles. In 2024 InCites Journal Citation Reports, its 2024 IF is 9.0 (8.7, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.
About the Authors
Dr. Jie Zhou is currently an associate professor at the School of Pharmacy, Fujian Medical University, China. She has long been engaged in research on drug delivery systems. She has published multiple papers as first or corresponding author in internationally renowned journals such as Angewandte Chemie International Edition, Acta Biomaterialia, ACS Applied Bio Materials, and Chemical Communications.
Dr. Biting Zhou, an ophthalmologist at the First Affiliated Hospital of Fujian Medical University, China. She has long been engaged in clinical and basic research in the field of ophthalmology. Her work has been published as first/corresponding author in journals such as Cell Death & Disease, American Journal of Pathology, and International Immunopharmacology.
Dr. Nanwen Zhang is currently a professor at the School of Pharmacy, Fujian Medical University, China. He has long been engaged in research on anti-inflammatory and immunopharmacology. He has published 20 papers as first or corresponding author in internationally renowned journals such as Chemico-Biological Interactions, International Immunopharmacology, and Acta Materia Medica.
Dr. Juhua Yang is currently a professor at the School of Pharmacy, Fujian Medical University, China. He focuses on the genetics of ocular diseases and the development of novel antibody therapeutics. He has published 58 academic papers, authored 1 monograph, and been granted 3 invention patents.
Dr. Xiaole Chen serves as Deputy Director of the Office of Scientific Research and Vice Dean of the School of Pharmacy at Fujian Medical University. Dr. Chen is committed to the research of biopharmaceutical drugs for ocular and autoimmune diseases. As Principal Investigator, he has been awarded several research grants, including the Young Scientists Fund of the National Natural Science Foundation of China (NSFC). He has authored or co-authored over 20 SCI-indexed papers as first or corresponding author and holds 3 authorized national invention patents.
Nano Research
Dithiolane-based antibody eyedrops for noninvasive treatment of corneal neovascularization
28-Nov-2025