Targeted delivery of rhein via hyaluronic acid modified liposomes for suppression of growth and metastasis of breast cancer

Targeting and suppressing the malignant growth and metastasis of breast cancer has been challenging for years. Herein, a nanocarrier based on hyaluronic acid (HA)-modified cationic liposomes was developed for targeted delivery of rhein to achieve breast cancer therapy. The optimum HA-Lip-rhein had spherical and core-shell-like morphologies with an appropriate size of 189.7 ± 5.2 nm. Moreover, the HA-Lip-rhein exhibited higher cellular uptake in 4 T1 cells and enhanced cytotoxicity compared with unmodified liposomal rhein. Furthermore, in vitro cell migration and invasion inhibition assays showed that the HA-Lip-rhein exhibited superior inhibitory effects on breast cancer metastasis. HA-Lip-rhein improved the tumor targeting ability, anti-breast cancer activity, with good safety profile in the 4 T1 breast cancer-bearing mice compared with free rhein and Lip-rhein. The appearance of metastatic tumor nodules in the lungs and H&E staining of liver and lung organs confirmed that HA-Lip-rhein exerted strong antitumor efficacy and inhibited distant metastasis of breast cancer. Overall, the developed HA-Lip-rhein exhibited a good antitumor effect and suppression effect of distant metastasis, making it a novel and promising nanoplatform for further development.