Study of the Efficacy and Multidrug Resistance Using Gold Nanoparticles-Based Drug Delivery Versus Conventional Chemotherapy in Non-Small-Cell Lung Cancer Cell Line

Abstract

Background: Cisplatin is the main chemotherapy in the treatment of non-small-cell lung cancer (NSCLC) combined with gemcitabine or other agents. Aim: The aim of this study was to evaluate in vitro the anti-tumor efficacy and multidrug resistance of gold nanoparticles (GNPs) conjugated with cisplatin and /or gemcitabine for the treatment of NSCLC. Methods: MTT cytotoxicity assay was carried out in NSCLC cell line (A549). Cell viabilities were determined after treatment with different concentrations of cisplatin, gemcitabine, GNPs-cisplatin or GNPs-gemcitabine. Combinations of variable ratios (1:1, 1:2, 2:1, 1:9, 9:1) of cisplatin + gemcitabine, GNPs-cisplatin + gemcitabine, cisplatin + GNPs-gemcitabine or GNPs-cisplatin + GNPs-gemcitabine were also tested. The Combination Index was computed for each combination concentration ratio and dose to know the best synergistic effect. Histological changes and multidrug resistance were studied. Results: The 1:1 ratio combination concentration showed the highest synergistic effect among all concentration ratios (p < 0.001). Multidrug resistance revealed that the percent efflux of the GNPs-cisplatin + GNPs-gemcitabine combination with a 1:1 ratio was the minimal in comparison to the other drug combinations. Conclusion: The use of nanoparticles functionalized with cytotoxic drugs such as cisplatin or gemcitabine alone or in combination enhances their antitumor effect and decreases the multidrug resistance in NSCLC cell line.