Hyaluronic acid-modified liposomal honokiol nanocarrier: Enhance anti-metastasis and antitumor efficacy against breast cancer

•Hyaluronic acid functionalization endows the liposomes to actively target tumor cells.•Honokiol shows great promise in breast cancer therapy, both in vitro and in vivo.•The nano-liposomes enhance anti-metastasis and antitumor efficacies against breast cancer. In an effort to enhance antitumor and anti-metastasis of breast cancer, honokiol (HNK) was encapsulated into hyaluronic acid (HA) modified cationic liposomes (Lip). The prepared HA-Lip-HNK had a spherical shape with a narrow size distribution. The enhanced antitumor efficacy of HA-Lip-HNK was investigated in 4T1 cells in vitro, wherein flow cytometry and confocal microscopy analysis revealed its HA/CD44-mediated greater cellular internalization. As anticipate, the significant cytotoxicity of the HA-Lip-HNK was also observed in 4T1 tumor spheroids. Furthermore, the superior prevention of tumor metastasis by HA-Lip-HNK was verified by in vitro anti-invasion, wound healing and anti-migration assessments, and in vivo bioluminescence imaging in pulmonary metastasis model. Finally, compared with unmodified liposomes, the HA-Lip-HNK exhibited higher tumor accumulation, and achieved a tumor growth inhibition rate of 59.5 %. As a result, the HA-Lip-HNK may serve as a promising tumor-targeted drug delivery strategy for the efficient therapy of metastatic breast cancer.