Raloxifene nano-micelles effect on triple-negative breast cancer is mediated through estrogen receptor-β and epidermal growth factor receptor

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that differs in progression, recurrence, and prognosis from other forms of breast cancer. The heterogeneity of TNBC has remained a challenge as no targeted therapy is currently available. Previously, we and others have demonstrated that raloxifene, a selective oestrogen receptor modulator, was also acting independently of the oestrogen receptor-α. However, raloxifene is characterised by a low bioavailability in vivo. Thus, we encapsulated raloxifene into a styrene-maleic acid (SMA) micelle to improve its pharmacokinetics. The micellar raloxifene had higher cytotoxicity when compared to the free formulation, promoted a higher cellular uptake and affected critical signalling pathways. Furthermore, SMA-raloxifene reduced TNBC tumour growth more efficiently than free raloxifene. Finally, we showed that this effect was partially mediated through oestrogen receptor-β. In conclusion, we have provided new insight into the role of raloxifene nanoformulation in improving the management of TNBC.

Keywords:

• Triple-negative breast cancer
• raloxifene
• nanomedicine
• micelle
• oestrogen receptor-β
• SERM
• EGFR

Disclosure statement

The authors acknowledge no financial interest or benefit that has arisen from the direct applications of this research.

Additional information

Funding

This work was supported by the Emerging Researcher First Grants from the Health Research Council of New Zealand under Grant 11–695 and Arabian Gulf University.