LAUSR

&NA; The objective of the present study was to investigate the effect of tamoxifen (Tam) loaded solid lipid nanoparticles (SLNs) on MCF7 Tam‐resistant breast cancer cells (MCF7‐TamR). Tam‐SLNs were produced by the hot homogenization method. The characterization studies of Tam‐SLNs demonstrated good physical stability with small particle size. The in vitro cytotoxicity results showed that Tam‐SLNs enhanced the efficacy of Tam and reversed the acquired Tam resistance by inducing apoptosis, altering the expression levels of specific miRNA and the related apoptosis‐associated target‐genes in both MCF7 and MCF7‐TamR cells without damaging the MCF10A control cells (p < 0.05). In conclusion, we demonstrated a molecular mechanism of the induction of apoptosis by Tam‐SLNs in MCF7 and MCF7‐TamR cells, and thus, we demonstrated that Tam‐SLNs were more effective than Tam. The present study suggests that the use SLNs may be a potential therapeutic strategy to overcome Tam‐resistance in breast cancer for clinical use. Graphical abstract Tam‐SLNs could potentially overcome Tam‐resistance by inducing apoptosis in breast cancer. Figure. No Caption available.