Although taxinine (Ta) is a natural compound with potential anti-hepatocellular carcinoma (HCC) activity, its low water solubility and delivery efficiency significantly limit its clinical application. To overcome this limitation, this study synthesized biotinylated chitosan (BCC) as a carrier and combined it with mesenchymal stem cell-derived exosomes (Exo). The ultrasonic method was utilized to prepare Ta-BCC Hybrid Nanovesicles (Exo@Ta-BCC), to enhance the tumor targeting of Ta and improve the therapeutic effect on HCC. The in vitro characterization results showed that the optimized Exo@Ta-BCC had a particle size of approximately 185.19 nm, a polydispersity index of 0.167, and a spherical shape observed via transmission electron microscopy. The in vitro release results indicate that the combination of ultrasound and Exo@Ta-BCC could significantly increase cumulative release rate of Ta. The cell uptake experiment confirmed that combination of ultrasound and Exo@BCC could effectively promote uptake of the drug by HepG2 cells. The in vitro efficacy study demonstrated that treatment of Exo@Ta-BCC with ultrasound had the strongest inhibitory effect on HepG2 cells. Additionally, in the nude mouse tumor model, the group treated with ultrasound combined with Exo@Ta-BCC showed the best therapeutic effect. In conclusion, the drug delivery system of ultrasound combined with Exo@BCC greatly improved solubility of Ta and endowed it with tumor targeting, thus making it possible for Ta to become a potential clinical drug for treatment of HCC.
Wan et al. (Mon,) studied this question.