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

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.