A paclitaxel-based supramolecular hydrogel loaded with mifepristone for the inhibition of breast cancer metastasis.

Breast cancer is the leading cause of cancer death among women and almost all of the breast cancer-caused mortality is related to metastasis. It has been reported that glucocorticoid facilitates the metastasis of breast cancer in mice, and mifepristone can antagonize the effect of glucocorticoid. Paclitaxel is one of the important drugs in the treatment of breast cancer. Mifepristone combined with paclitaxel may be an effective strategy for anti-metastasis of breast cancer. However, the inherent defects of them in short blood circulation half-life and lack of tumor targeting not only limit their effectiveness but also cause adverse reactions. Therefore, our aim is to explore a novel protocol against breast cancer metastasis, further optimize its therapeutic efficacy by nano-delivery system, and initially explore its mechanism. Herein, a paclitaxel-conjugated and mifepristone-loaded hydrogel (PM-nano) was prepared by self-assembly. Its characterizations were studied. The anti-metastasis effect was also evaluated in vitro and in vivo. Its mechanism was also explored by western blot assay. The resulted PM-nano was developed with favorable water solubility and good biocompatibility. Moreover, PM-nano displayed increased cell uptake property and stimulated drug release in tumor micro-acidic environment. PM-nano was more effective in inhibiting the proliferation and metastasis of breast cancer than other groups in vitro and in vivo. PM-nano might inhibit metastasis through glucocorticoid receptor/receptor tyrosine kinase-like orphan receptor 1 and matrix metalloproteinases. Taken together, PM-nano exhibited superior anti-metastasis effect against breast cancer and excellent biocompatibility in vitro and in vivo, providing a new option for anti-metastasis.