Co-delivery of metformin and silibinin in dual-drug loaded nanoparticles synergistically improves chemotherapy in human non-small cell lung cancer A549 cells

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Combination of nanoparticle (NP)-based therapeutic methods with chemotherapy has suggested a potent strategy to increase the intracellular concentrations of drugs and enhance synergistic effects in several malignancies including lung cancer therapy. Here, Metformin (Met) and Silibinin (Sil) as two well-known natural herbal compounds were co-loaded into polymeric nanoparticles composed of poly (D, l -lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) and studied the synergistic inhibitory effect of these compounds against A549 human lung cancer cells. The size and morphology were determined using SEM and DLS. Characterization of NPs were performed using FTIR, entrapment efficiency and drug release. In addition, MTT assay, DAPI staining, and qRT-PCR were used to evaluate the cytotoxicity of both individual and combined form of drugs in A549 lung cancer cells. Uniformity in size and shape of NPs with a mean diameter of approximately 60 nm confirmed by SEM. The IC 50 of Met-NPs, Sil-NPs and dual-drug loaded NPs were 36.11, 9.75, and 0.85 μM, respectively, which was much lower than that of pure forms. MTT assay revealed that dual-drug loaded NPs had a significant synergistic cytotoxicity against A549 lung carcinoma cells in comparison with other groups. Furthermore, the results demonstrated that dual-drug loaded NPs could induce apoptosis in A549 cancer cell by upregulation of caspase-3, caspase-7 and Bax (2-fold, 2-fold, 2.1-fold and 2.2-fold, respectively), along with Bcl-2, hTERT and Cyclin D1 down regulation (0.25-fold, 1.4-fold and). Ultimately, this study revealed that the combination of dual-drug loaded NPs with current cancer therapies holds promise for the potential of lung cancer treatment. • The NPs prolonged the Met and Sil release and improved extensively of its bioavailability. • The dual-drug loaded NPs manifested a significant dose-dependent inhibitory effect against A549 cells. • Using dual-drug loaded NPs may be an efficient strategy for the effective treatment of lung cancer.