Zhu Siqing, Huang Huiying, Liu Dong, Wen Shimin, Shen Liangliang, Lin Quankui
Department of Biomaterials, School of Ophthalmology & Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, PR China.
Bioact Mater. 2022 Feb 26;15:469-481. doi: 10.1016/j.bioactmat.2022.02.019. eCollection 2022 Sep.
Posterior capsular opacification (PCO), the most common complication after cataract surgery, is caused by the proliferation, migration and differentiation of residual lens epithelial cells (LECs) on the surface of the intraocular lens (IOL). Although drug-loaded IOLs have been successfully developed, the PCO prevention efficacy is still limited due to the lack of targeting and low bioavailability. In this investigation, an exosome-functionalized drug-loaded IOL was successfully developed for effective PCO prevention utilizing the homologous targeting and high biocompatibility of exosome. The exosomes derived from LECs were collected to load the anti-proliferative drug doxorubicin (Dox) through electroporation and then immobilized on the aminated IOLs surface through electrostatic interaction. In vitro experiments showed that significantly improved cellular uptake of Dox@Exos by LECs was achieved due to the targeting ability of exosome, compared with free Dox, thus resulting in superior anti-proliferation effect. In vivo animal investigations indicated that Dox@Exos-IOLs effectively inhibited the development of PCO and showed excellent intraocular biocompatibility. We believe that this work will provide a targeting strategy for PCO prevention through exosome-functionalized IOL.
后囊膜混浊（PCO）是白内障手术后最常见的并发症，由眼内晶状体（IOL）表面残留的晶状体上皮细胞（LEC）增殖、迁移和分化引起。尽管载药IOL已成功研发，但由于缺乏靶向性和低生物利用度，其预防PCO的效果仍然有限。在本研究中，利用外泌体的同源靶向性和高生物相容性，成功研发了一种外泌体功能化的载药IOL，用于有效预防PCO。收集来源于LEC的外泌体，通过电穿孔加载抗增殖药物阿霉素（Dox），然后通过静电相互作用固定在胺化IOL表面。体外实验表明，与游离Dox相比，由于外泌体的靶向能力，LEC对Dox@Exos的细胞摄取显著提高，从而产生了更好的抗增殖效果。体内动物研究表明，Dox@Exos-IOLs能有效抑制PCO的发展，并表现出优异的眼内生物相容性。我们相信，这项工作将为通过外泌体功能化IOL预防PCO提供一种靶向策略。
