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.