Gingerol/letrozole-loaded mesoporous silica nanoparticles for breast cancer therapy: In-silico and in-vitro studies

In this study, in-silico properties of Gingerol (Gin) and Letrozole (Let), as two potential anti-cancer drugs, were investigated and some significant ADME drawbacks were predicted. Accordingly, to address the drawbacks, mesoporous silica nanoparticles (MSNs) were prepared, functionalized with zinc, amine, and graphene oxide (GO) (MZNG), and employed for loading and delivery of the both to breast cancer cells in-vitro. Biophysical analysis showed that Let and Gin-loaded MZNGs have spherical structure with a mean diameter of ~210 nm. The MZNGs provided high entrapment efficiency of Let and Gin with a pH-sensitive sustained release profile. The cytotoxicity assay demonstrated that loading of the drugs into MZNG significantly improves their inhibitory effects on the breast cancer cells, which was attributed to enhanced cellular uptake. Inhibition of cancer cell proliferation and cell arrest in G0/G1 phase was due to the regulation of the expression levels of the studied genes in breast cancer cells. Upon treatment with the drugs, a downregulation for Bcl-2, MMP-2, MMP-9, CyclinD and CyclinE genes, and an upregulation for Bax, Caspase3 and Caspase9 genes were observed. Furthermore, the Let/Gin-loaded MZNG inhibited migration and invasion in the breast cancer cells. Our results suggested that MZNG provided a suitable and efficient nanosystem for co-delivery of Let and Gin with synergic effect. The Let/ Gin-loaded MZNG induced apoptosis and inhibition of migration and proliferation in the breast cancer cells. Overall, the prepared nano-formulation holds a great promise for the treatment of not only breast cancer but also other cancers.