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Safety and toxic effects of nanoparticles are still largely unexplored due to the multiple aspects that influence their behaviour toward biological systems. Here, we focus the attention on 12 nm spherical gold nanoparticle coated or not with hyaluronic acid compared to its precursor counterpart salt. Results ranging from the effects of a 10-days exposure in an in vitro model with BALB/c 3T3 fibroblast cells show how 12 nm spherical gold nanoparticles are internalized from 3T3 cells by endo-lysosomal pathway by an indirect measurement technique; and how gold nanoparticles, though not being a severe cytotoxicant, induce DNA damage probably through an indirect mechanism due to oxidative stress. While coating them with hyaluronic acid reduces gold nanoparticles cytotoxicity and slows their cell internalization. These results will be of great interest to medicine, since they indicate that gold nanoparticles (with or without coating) are suitable for therapeutic applications due to their tunable cell uptake and low toxicity.

Water soluble gold nanoparticles were synthesized in a single step using a double layer of a gemini imidazolium-based amphiphile as both reagent and stabilizer. The synthetic strategy exploits the amphiphilic nature of the ligand, and different ratios of ligand to Au(III) precursor were tested in order to favour the formation of amphiphile bilayer-coated nanoparticles, as indicated by their solubility and the thermogravimetric analysis, which proved the gold/organic ratio. The approximately 10 nm nanoparticles display cytotoxicity on Caco-2 cells similar to gold nanomaterials coated with other cationic surfactants, mainly because of their bilayer coating. Instead, genotoxicity was proven to be low, and the gold nanoparticles showed cell internalization being able to leave endosomes and without entering the nuclei. The incorporation of piroxicam, a poorly water soluble drug that has anti-inflammatory and antitumoral activity, was achieved thanks to anion binding by the amphiphile. Subsequently in vitro release of piroxicam from these nanoparticles was demonstrated, indicating their potential in combined chemotherapy.

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