Abstract
Aim: Gold nanoparticles (GNPs) are intended to be used in nanomedicine. Due to nanotechnology innovation GNPs of variable sizes and in different shapes including rods, spheres, cubes, etc., can easily be produced. The aim of the present studies was to evaluate the cyto- and genotoxicity inducible by different shaped GNPs on normal human peripheral blood lymphocytes.
Methods: Four different shapes of GNPs including big rod GNPs (BR-GNPs, 50 nm), small rod GNPs (SR-GNPs, 30 nm), sphere GNPs (S-GNPs, 15 nm) and semi-cube GNPs (SC-GNPs, 15 nm) were studied. Cultured human blood lymphocytes were treated with different concentrations of these GNPs for 24 h in vitro. Cytotoxicity was evaluated based on the mitotic index (MI), while genotoxicity was studied by an interphase-fluorescence in situ hybridization (I-FISH) assay. The following genes were studied in I-FISH: TP53, CASP3, CASP7, CASP9, TNF and CRP. The induction of cell death was investigated using the apoptotic-necrotic assay.
Results: The lowest concentration of BR-GNPs neither had an effect mitotic activity nor enhanced gain or loss of examined gene signals in a significant manner with I-FSH. Other concentrations of BR-GNPs, SR-GNPs, S-GNPs and SC-GNPs with all concentrations inhibited the mitotic activity of the cells and reduced the cell proliferation highly significantly. The different types of GNPs initiated the duplication of CASP3, CASP7 and CASP9 besides TP53 genes; however they reduced the signals of TNF and CRP genes highly significantly as supported by I-FISH results. The apoptotic-necrotic assay demonstrated that small rod, sphere and semi-cube GNPs enhanced the cell death rate through the apoptotic pathway.
Conclusion: GNPs at high concentration can reduce the cell proliferation and induce DNA damage. Low concentration of rod-shaped GNPs at 50 nm was safe on human lymphocytes. Further research studies are required to optimize the concentration, shape and size of GNPs before using them in nanomedicine.