Thermoresponsive polymer encapsulated HT1080 exosomes lyse localized blood clot: A preclinical evaluation in rat carotid artery thrombosis model

Since tissue plasminogen activators have limitations, an alternate therapeutic agent is needed with similar clot lysis activity and better stability to degrade thrombus. We have identified HT1080 fibrosarcoma cell-derived exosomes having clot-busting potential, which aided in healing of endothelial cells in presence of ischemia. These exosomes were encapsulated in a thermoresponsive polymer to regulate their release. In this study, exosomes released from the gel (100–150 nm in diameter) were functional and biocompatible with endothelial cells when combined with thermoresponsive polymer. A ferric chloride-induced rat carotid artery thrombosis model was used for preclinical testing. Ultrasound imaging showed considerable clot removal after 5 days, with vessel diameter between 0.9- and 1-mm. Histological staining demonstrated few fibrin clots in treatment groups. Finally, CD31 immunohistochemical staining showed that the therapy regenerated endothelial lining. As a result, our smart polymeric exosome releasing composite could be a possible therapeutic method for vascular disease prevention.