Combination Nanomedicine Strategy for Preventing High-Risk Corneal Transplantation Rejection

作者：Tuo Meng, Jinhua Zheng, Crystal S. Shin, Nan Gao, Divya Bande, Hadi Sudarjat, Woon N. Chow, Matthew S. Halquist, Fu-Shin Yu, Ghanashyam Acharya, Qingguo Xu · 发表于：ACS Nano · 年份：2024 · DOI：10.1021/acsnano.4c06595 · 被引用次数：11 · 研究领域：Corneal Surgery and Treatments、Ocular Surface and Contact Lens、Corneal surgery and disorders

High-risk (HR) corneal transplantation presents a formidable challenge, with over 50% of grafts experiencing rejection despite intensive postoperative care involving frequent topical eyedrop administration up to every 2 h, gradually tapering over 6-12 months, and ongoing maintenance dosing. While clinical evidence underscores the potential benefits of inhibiting postoperative angiogenesis, effective antiangiogenesis therapy remains elusive in this context. Here, we engineered controlled-release nanomedicine formulations comprising immunosuppressants (nanoparticles) and antiangiogenesis drugs (nanowafer) and demonstrated that these formulations can prevent HR corneal transplantation rejection for at least 6 months in a clinically relevant rat model. Unlike untreated corneal grafts, which universally faced rejection within 2 weeks postsurgery, a single subconjunctival injection of the long-acting immunosuppressant nanoparticle alone effectively averted graft rejection for 6 months, achieving a graft survival rate of ∼70%. Notably, the combination of an immunosuppressant nanoparticle and an anti-VEGF nanowafer yielded significantly better efficacy with a graft survival rate of >85%. The significantly enhanced efficacy demonstrated that a combination nanomedicine strategy incorporating immunosuppressants and antiangiogenesis drugs can greatly enhance the ocular drug delivery and benefit the outcome of HR corneal transplantation with increased survival rate, ensuring patient compl...