Treatment for Hepatocellular Carcinoma Is Enhanced When Norcantharidin Is Encapsulated in Exosomes Derived from Bone Marrow Mesenchymal Stem Cells

Mesenchymal stem cell-derived exosomes (MSC-Exos) have potential as drug-delivery vehicles and exhibit great promise for hepatocellular carcinoma (HCC) therapy. Here, we consider bone mesenchymal stem cell-derived exosomes (BMSC-Exos) as drug carriers to encase anticancer drug norcantharidin (NCTD) and explore their potential therapeutic effects against HCC. NCTD was loaded into purified exosomes from BMSCs via electroporation, and an in vitro drug release study showed that BMSC-Exos-NCTD provided a continuous and slow release of the drug. A series of in vitro and in vivo pharmacodynamic evaluations based on the HCC cell line HepG2 were conducted. The results showed that the BMSC-Exos-NCTD delivery system effectively promoted cellular uptake, induced cell cycle arrest, reduced tumor cell proliferation, increased apoptosis, and exerted obvious in vivo antitumor effects compared with the NCTD treatment alone, with BMSC-Exos-NCTD showing more significant antitumor effects. Furthermore, the in vivo detection results of the homing effect using the probe Cy5.5 showed that the BMSC-Exos carrier has an in situ homing effect on the tumor sites of HCC in mice. Moreover, BMSC-Exos-NCTD did not show body toxicity. Excitedly, BMSC-Exos-NCTD repaired damaged liver tissues in liver sections; specifically, the experimental effectiveness of the exosomes on the normal liver cell line L02 indicated that the damaged liver cells were repaired by the exosomes, as reflected by the increase in cellular proliferation and the inhibition of liver cell oxidation. Our results suggest that BMSC-Exos, as drug carriers with specific functions, have great potential in the HCC treatment in combination with anticancer drugs.