PDF(Pubmed)
Abstract：
Proliferative vitreoretinopathy (PVR) is a common cause of vision loss after retinal reattachment surgery and ocular trauma. The key pathogenic mechanisms of PVR development include the proliferation, migration and epithelial-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPEs) activated by the growth factors and cytokines after surgery. Although some drugs have been tried in PVR treatments as basic investigations, the limited efficacy remains an obstacle, which may be due to the single pharmacological action and lack of targeting. Herein, the anti-proliferative Daunorubicin and anti-inflammatory Dexamethasone were co-loaded in the RPEs-derived exosomes (Exos), obtaining an Exos-based dual drug-loaded nanocarrier (Exos@D-D), and used for multiple PVR therapy. Owing to the advantages of homologous Exos and the dual drug loading, Exos@D-D showed good RPEs targeting as well as improved uptake efficiency, and could inhibit the proliferation, migration, as well as EMT of RPEs effectively. The animal studies have also demonstrated that Exos@D-D effectively inhibits the production of proliferative membranes and prevents the further development of inflammation, shows significant therapeutic effects on PVR and good biocompatibility. Such Exos-based dual drug-loaded nanocarrier investigation not only provides a promising approach for multifunctional exosome drug delivery systems construction, but also has great potential in PVR clinical therapy application.
摘要：
增生性玻璃体视网膜病变（PVR）是视网膜复位手术和眼外伤后视力丧失的常见原因。PVR发生的关键致病机制包括增殖,生长因子和细胞因子激活的视网膜色素上皮细胞（RPEs）在手术后的迁移和上皮间质转化（EMT）。尽管一些药物已经在PVR治疗中尝试作为基础研究，有限的功效仍然是一个障碍，这可能是由于单一的药理作用和缺乏靶向。在这里，抗增殖柔红霉素和抗炎地塞米松共同负载在RPEs衍生的外泌体（Exos）中，获得基于Exos的双载药纳米载体(Exos@D-D)，用于多种PVR治疗。由于同源Exos的优点和双重载药量,Exos@D-D显示出良好的RPE靶向性以及提高的摄取效率，并且可以抑制增殖，迁移,以及有效的RPEEMT。动物研究还表明，Exos@D-D有效抑制增殖膜的产生，并防止炎症的进一步发展，对PVR具有显著的治疗效果和良好的生物相容性。这种基于Exos的双载药纳米载体研究不仅为多功能外泌体药物递送系统的构建提供了有希望的方法。而且在PVR临床治疗中也有很大的应用潜力。
