Abstract
Background
Platinum-based drugs are widely used in cancer therapy, but are known for toxic side effects and resistance. Combinational drug delivery represents an effective chemotherapeutic strategy, but often leads to an increased toxicity. Aim of this study is to test the co-delivery of cisplatin with natural antioxidants on hierarchial porous large surface area hexagonal nanocarriers for synergistic action.
Results
A series of structured mesoporous materials were impregnated with magnetic spinel ferrite (30% CuFe
2
O
4
) and then coated with curcumin (25% wt/wt). Mesosilicalite and MCM-41 with high curcumin release abilities were functionalized with cisplatin (5% wt/wt) for synergistic effect of combinational drugs. The cytotoxic efficiency of our nanocomposites was tested on cell viability of MCF7 (human breast cancer), human cervical cancer (HeLa), colorectal cancer (HCT116), and HFF (human foreskin fibroblasts) cell lines using the MTT cell viability assay. At a concentration of 0.1 mg/ml, CuFe
2
O
4
/mesosilicalite/curcumin/cisplatin resulted in 89.53% reduction in viability in MCF7, 94.03% in HeLa, 64% in HCT116 and 87% in HFF; whereas, CuFe
2
O
4
/MCM-41/curcumin/cisplatin resulted in 76% reduction in viability in MCF7, 64.46% in HeLa, 64% in HCT116 and 24% in HFF. The EC
50
for CuFe
2
O
4
/mesosilicalite/curcumin/cisplatin was 81.23 µg/ml in MCF7, 47.55 µg/ml in HeLa, 48.96 µg/ml in HCT116 and 76.83 µg/ml in HFF. The EC
50
for CuFe
2
O
4
/MCM-41/curcumin/cisplatin was 72.51 µg/ml in MCF7, 58.6 µg/ml in HeLa, 62.58 µg/ml in HCT116 and 154.2 µg/ml in HFF. Furthermore, cells treated with both nanocomposites had a high number of cleaved Caspase 3-positive cells suggesting that the reduction in cell viability was triggered by activating the apoptotic signaling pathway.
Conclusion
Our results show that CuFe
2
O
4
/MCM-41/curcumin/cisplatin is a better candidate for combinational drug therapy due to its lowest EC
50
value and the wider difference in EC
50
(a fold change) between cancerous and non-cancerous cell line.