Improved chemo-photothermal therapy of hepatocellular carcinoma using chitosan-coated gold nanoparticles

A green method was used for producing gold nanoparticles (Au NPs) using chitosan as a natural cationic, biodegradable and biocompatible polymer. In this method, chitosan acts as a reducing and stabilizing agent for the synthesis of Au NPs. Different concentrations of chitosan solutions (0.01%, 0.05%, 0.1%, 0.2%, 0.5% and 1%) were applied. In an attempt to mitigate the side effects of anti-cancer drug, 5-fluorouracil (5-FU), through reducing drug doses in photothermal therapy, the formed positively-charged chitosan-wrapped Au NPs were used as a drug delivery system for negatively charged 5-FU to hepatocellular carcinoma cells (HepG2). Au NPs as well as 5-FU@Au nanocomposites were characterized with UV-VIS spectroscopy, particle size, zeta potential, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and High-Performance Liquid Chromatography (HPLC). The chitosan concentration was shown to be an important parameter for optimizing the dispersion of Au NPs and 5-FU@Au nanocomposites over long time. This stability offers the 5-FU@Au nanocomposites as good candidate for cancer treatment with reduced drug doses in photothermal therapy. A 72% loading-efficiency of 5-FU was obtained. Cytotoxic assay was carried out on HepG2 cell line and it reveals the effectiveness of 5-FU@Au nanocomposites in the presence and absence of laser irradiation compared with the free 5-FU. The cytotoxicity effect of free 5-FU and 5-FU@AuNPs nanocomposites was studied, and it was found that the concentration of 5-FU@Au nanocomposites required to attain 50% of inhibition growth rate was lower than that of free 5-FU in absence of laser radiation and was much lower in presence of laser radiation.