A Natural Membrane Vesicle Exosome-based Sinomenine Delivery Platform for Hepatic Carcinoma Therapy

Background: Recent evidence has been demonstrated that Sinomenine (SIN) exerts antitumor activity in vitro. However, the clinical utility of SIN remains limited mainly because of its poor bioavailability. Exosomes are nanoscale vesicles that play crucial roles in intracellular communications through functionally active substances such as DNA and RNA. Exosomes have been utilized as nanocarriers for targeted drug delivery of different anticancer drugs. Methods: The present study aimed to evaluate the effectiveness of combined Exosomes-SIN for the treatment of hepatocellular carcinoma (HCC) in a rat model. To do so, we prepared a mixture of SIN and exosomes (Exo-SIN) to improve the bioavailability of SIN to treat liver cancer. The in vitro releasing profile of the Exo-SIN was examined. Results: We observed a continuous, slow release of SIN from Exo-SIN in simulated body fluid as well as tumor microenvironment. In the cytotoxicity test, Exo-SIN exhibited a significantly stronger inhibition in HepG2 cells compared to free SIN. The flow cytometry assessments showed that Exo-SIN could suppress HepG2 cell migration in a Transwell assay and induce cell cycle arrest and cellular apoptosis. Western blotting showed that survivin, a crucial protein for the survival of living cells, was significantly downregulated after treatment with Exo-SIN. Conclusion: In conclusion, our data suggested that Exo-SIN could serve as a potential, effective delivery platform for hepatic carcinoma therapy.