Augmented cellular uptake and homologous targeting of exosome-based drug loaded IOL for posterior capsular opacification prevention and biosafety improvement

Abstract

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.