Co-Delivery of Silymarin and Metformin Dual-Loaded in Mesoporous Silica Nanoparticles Synergistically Sensitizes Breast Cancer Cell Line to Mitoxantrone Chemotherapy

The development nano-carriers based therapeutic methods is a potent strategy for enhancing cellular delivery of drugs and therapeutic efficiency in cancer chemotherapy. In the study, silymarin(SLM) and metformin (Met) were co-loaded into mesoporous silica nanoparticles (MSNs) and evaluated the synergistic inhibitory effect of these natural herbal compound in improving chemotherapeutic efficiency against MCF7MX and MCF7 human breast cancer cells. Nanoparticles have been synthesized and characterized by FTIR, BET, TEM, SEM, and X-ray diffraction. Drug loading capacity and release determined. The both single and combined form of SLM and Met (free and loaded MSN) were used for MTT assay, colony formation and real time-PCR in cellular study. The synthesis MSN were uniformity in size and shape with particle size of approximately 100 nm and pore size of approximately 2 nm. The Met-MSNs IC30, SLM -MSNs IC50 and dual-drug loaded MSNs IC50 were much lower than of free-Met IC30, free-SLM IC50 and free Met-SLM IC50 MCF7MX and MCF7cells. The co-loaded MSNs treated cells were increased sensitivity to mitoxantrone with the inhibition of BCRP mRNA expressions and could induce apoptosis in MCF7MX and MCF7 cells in comparison with other groups. Colony numbers were significantly reduced in comparison to with other groups in the co-loaded MSNs -treated cells ( ${p} < 0.01$ ). Our results indicate that Nano-SLM enhances the anti-cancer effects of SLM against human breast cancer cells. The findings of the present study suggest that the anti-cancer effects of both metformin and silymarin enhances against breast cancer cells when MSNs are used as a drug delivery system.