Synergistic and enhanced anticancer effect of a facile surface modified non-cytotoxic silver nanoparticle conjugated with gemcitabine in metastatic breast cancer cells

Abstract

The safety and efficacy of metallic nanoparticles was one of the major challenges that limit their use in the treatment of cancer. Nanotechnology is applied in the field of pharmaceutical sciences with focus on improving the therapeutic outcome in various diseases. Recently, many novel nano-formulations comprising two or more drugs were studied to improve their efficacy with better safety profile. In this study, we investigated the synergistic cytotoxic effect of gemcitabine (GEM) conjugated non-cytotoxic dose of silver nanoparticles (AgNP) in MDA-MB-453 human triple-negative metastatic breast cancer cells. Synthesized AgNP and electrostatic conjugates were characterized by UV-spectroscopy, dynamic light scattering (DLS), Transmission electron microscopy (TEM), Scanning electron microscopy (SEM) and energy dispersive x-ray analysis (EDAX). GEM-(non-cytotoxic AgNP) conjugated system (IC50 = 37.64 μM) showed better cytotoxic activity in MDA-MB-453 cells when compared to individual treatments of GEM (IC50 = 56.54 μM) or AgNP (IC50 = 71.45 μg/ml). The synergism between the GEM-(non-cytotoxic AgNP) for all the tested doses were evaluated using CompuSyn software. The combination index (CI) of ED50, ED75 and ED90 showed synergism for GEM-(non-cytotoxic AgNP) conjugation. According to the calculated dose reduction index (DRI), it requires 1.70-fold less GEM plus 42.55-fold less AgNP to achieve the same 50 % inhibition at 18.38 (GEM): 1 (AgNP) ratio.