In the present study, a magnetic niosomal nanocarrier for co-delivery of
curcumin and
letrozole into
breast cancer cells has been designed. The magnetic
NiCoFe2O4 core was coated by a thin layer of
silica, followed by a niosomal structure, allowing us to load
letrozole and
curcumin into the
silica layer and niosomal layer, respectively, and investigate their synergic effects on
breast cancer cells. Furthermore, the nanocarriers demonstrated a pH-dependent release due to the niosomal structure at their outer layer, which is a promising behavior for
cancer treatment. Additionally, cellular assays revealed that the nanocarriers had low cellular uptake in the case of non-tumorigenic cells (i.e., MCF-10A) and related high viability but high cellular uptake in
cancer cell lines (i.e., MDA-MB-231 and SK-BR-3) and related low viability, which is evidenced in their high cytotoxicity against different
breast cancer cell lines. The cytotoxicity of the
letrozole/
curcumin co-loaded nanocarrier is higher than that of the aqueous solutions of both drugs, indicating their enhanced cellular uptake in their encapsulated states. In particular,
NiCoFe2O4@L-
Silica-L@C-
Niosome showed the highest cytotoxicity effects on MDA-MB-231 and SK-BR-3
breast cancer cells. The observed cytotoxicity was due to regulation of the expression levels of the studied genes in
breast cancer cells, where downregulation was observed for the Bcl-2,
MMP 2,
MMP 9,
cyclin D, and
cyclin E genes while upregulation of the expression of the Bax,
caspase-3, and
caspase-9 genes was observed. The flow cytometry results also revealed that
NiCoFe2O4@L-
Silica-L@C-
Niosome enhanced the apoptosis rate in both MDA-MB-231 and SK-BR-3 cells compared to the control samples. The findings of our research show the potential of designing magnetic niosomal formulations for simultaneous targeted delivery of both hydrophobic and hydrophilic drugs into
cancer cells in order to enhance their synergic chemotherapeutic effects. These results could open new avenues into the future of nanomedicine and the development of
theranostic agents.