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.

Keywords

• cisplatin
• gemcitabine
• multidrug resistance
• nanoparticles
• non-small cell lung cancer