Nano-encapsulated metformin-curcumin in PLGA/PEG inhibits synergistically growth and hTERT gene expression in human breast cancer cells

Abstract

The study was aimed at investigating the synergistic inhibitory effect of unique combinational regimen of nanocapsulated Metformin (Met) and Curcumin (Cur) against T47D breast cancer cells. For this purpose, Met and Cur were co-encapsulated in PEGylated PLGA nanoparticles (NPs) and evaluated for their therapeutic efficacy. The morphology and dynamic light scattering (DLS) analyses were carried out to optimize the nanoformulations. Drug release study was performed using dialysis method and then the cytotoxic and inhibitory effect of individual and combined drugs on expression level of hTERT in T47D breast cell line were evaluated using MTT assay and qPCR, respectively. The results showed that free drugs and formulations exhibited a dose-dependent cytotoxicity against T47D cells and especially, Met-Cur-PLGA/PEG NPs had more synergistic antiproliferative effect and significantly arrested the growth of cancer cells than the other groups (p<.05). Real-time PCR results revealed that Cur, Met and combination of Met-Cur in free and encapsulated forms inhibited hTERT gene expression. It was found that Met-Cur-PLGA/PEG NPs in relative to free combination could further decline hTERT expression in all concentration (p<.05). Taken together, our study demonstrated that Met-Cur-PLGA/PEG NPs based combinational therapy holds promising potential towards the treatment of breast cancer.