Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China.
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200011, P. R. China.
Adv Healthc Mater. 2022 Jul;11(14):e2200283. doi: 10.1002/adhm.202200283. Epub 2022 May 27.
The eye is susceptible to viral infections, causing severe ocular symptoms or even respiratory diseases. Methods capable of protecting the eye from external viral invasion in a long-term and highly effective way are urgently needed but have been proved to be extremely challenging. Here, a strategy of forming a long-acting protective ocular surface is described by instilling adhesive dual-antiviral nanoparticles. Taking pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a model virus, antiviral agent-loaded nanoparticles are coated with a "double-lock" hybrid cell membrane abundant with integrin-β1 and angiotensin converting enzyme II (ACE2). After instillation, the presence of integrin-β1 endows coated nanoparticles with steady adhesion via specific binding to Arg-Gly-Asp sequence on the fibronectin of ocular epithelium, achieving durable retention on the ocular surface. In addition to loaded inhibitors, the exposure of ACE2 can trap SARS-CoV-2 and subsequently neutralize the associated spike protein, playing a dual antiviral effect of the resulting nanoparticles. Adhesive dual-antiviral nanoparticles enabled by coating with a "double-lock" hybrid cell membrane could be a versatile platform for topical long-acting protection against viral infection of the eye.
眼睛容易受到病毒感染，导致严重的眼部症状甚至呼吸道疾病。目前急需一种能够长期、高效地保护眼睛免受外部病毒入侵的方法，但已被证明极具挑战性。在这里，通过滴注粘性双抗病毒纳米粒子来描述形成长效保护性眼表的策略。以假型严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）为模型病毒，将载有抗病毒药物的纳米粒子包被上富含整合素-β1 和血管紧张素转换酶 II（ACE2）的“双锁”混合细胞膜。滴注后，整合素-β1 的存在通过与眼部上皮细胞纤连蛋白上的精氨酸-甘氨酸-天冬氨酸序列的特异性结合赋予包被纳米粒子稳定的粘附性，从而在眼表面实现持久保留。除了负载抑制剂外，ACE2 的暴露还可以捕获 SARS-CoV-2，并随后中和相关的刺突蛋白，从而发挥所得到的纳米粒子的双重抗病毒作用。通过“双锁”混合细胞膜包被的粘性双抗病毒纳米粒子可以成为一种用于眼部病毒感染的长效局部保护的多功能平台。
