Title:A Natural Membrane Vesicle Exosome-based Sinomenine Delivery Platform for Hepatic Carcinoma Therapy
Volume: 21
Issue: 14
Author(s): Ying Wang, Ling Zhao, Wanwen Yuan, Leyi Liang, Ming Li, Xuesong Yu*Yan Wang*
Affiliation:
- School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, 510006,China
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006,China
Keywords:
Exosomes, Natural nanoparticle, Sinomenine, Anticancer, Targeted drug delivery, Nanocarrier, Mechanism of action.
Abstract:
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.
