A Tumor-homing nanoplatform for the co-delivery of triptolide and siRNA-A4B2 conspicuously overcomes peritoneum metastasis of ovarian cancer.

BACKGROUND

Despite advances in ovarian cancer treatment, the tendency for cancer cells to metastasise to the peritoneum still results in poor prognosis. Studies have demonstrated that the integrin family plays a role in this metastasis; however, the underlying mechanism remains unclear. Triptolide (TP) has been confirmed to have a strong cytotoxic effect against ovarian cancer. However, its clinical application is limited by its severe systemic toxicity and low water solubility.

METHODS

This study investigated the integrins involved in peritoneal metastasis and their associated mechanisms. Furthermore, Si/TP@Exos were constructed to counteract the metastatic potential of ovarian cancer cells.

RESULTS

In vitro experiments showed that the construction of the ITGA4B2/AEP ternary complex contributed to the peritoneal metastasis of ovarian cancer by activating the IL-17 and NF-kappa B signalling pathways. Thus, whether the combined application of siRNA targeting ITGA4B2 and TP could further overcome peritoneal metastasis in ovarian cancer was investigated. In vitro results indicated that Si/TP@Exos were efficiently taken up by ovarian cancer cells, thus significantly enhancing the apoptosis of tumor cells. Similarly, Si/TP@Exos were effectively enriched in the tumor areas and exerted anti-tumor activity obviously in vivo.

CONCLUSIONS

Together, these findings present a novel strategy to overcome the peritoneal metastasis tendency of ovarian cancer and offer a potential therapeutic solution for clinical treatment of ovarian cancer. The combination of traditional Chinese medicine nano drug delivery platforms provides a new perspective for cancer treatment.