Effect of surface modification of silica nanoparticles on toxicity and cellular uptake by human peripheral blood lymphocytes in vitro.

Silica nanoparticles have an interesting potential in drug delivery, gene therapy and molecular imaging due to the possibility of tailoring their surface reactivity that can be obtained by surface modification. Despite these potential benefits, there is concern that exposure of humans to certain types of silica nanomaterials may lead to significant adverse health effects. The motivation of this study was to determine the kinetics of cellular binding/uptake of the vinyl- and the aminopropyl/vinyl-modified silica nanoparticles into peripheral blood lymphocytes in vitro, to explore their genotoxic and cytotoxic properties and to compare the biological properties of modified silica nanoparticles with those of the unmodified ones. Size of nanoparticles determined by SEM varied from 10 to 50 nm. The average hydrodynamic diameter and zeta potential also varied from 176.7 nm (+18.16 mV) [aminopropyl/vinyl-modified] and 235.4 nm (-9.49 mV) [vinyl-modified] to 266.3 (-13.32 mV) [unmodified]. Surface-modified silica particles were internalized by lymphocytes with varying efficiency and expressed no cytotoxic nor genotoxic effects, as determined by various methods (cell viability, apoptosis/necrosis, oxidative DNA damage, chromosome aberrations). However, they affected the proliferation of the lymphocytes as indicated by a decrease in mitotic index value and cell cycle progression. In contrast, unmodified silica nanoparticles exhibited cytotoxic and genotoxic properties at high doses as well as interfered with cell cycle.

The dose-response relationship for dicentric chromosomes and γ-H2AX foci in human peripheral blood lymphocytes: influence of temperature during exposure and intra- and inter-individual variability of donors.

PURPOSE: Hypothermia during in vitro irradiation of human peripheral blood lymphocytes (PBL) affects the level of chromosome aberrations. The molecular mechanisms of this phenomenon are not fully understood. The aim of our study was to examine the effect of hypothermia on the dose-response relationship for dicentric chromosomes and the level of γ-H2AX (phosphorylated histone H2AX) foci. In addition, the inter- and intra-individual variability was assessed in relation to temperature. MATERIALS AND METHODS: PBL were kept at 0.8, 20 and 37°C and then exposed to gamma-rays (from 0-3 Gy). Dicentric chromosomes were scored in first post-treatment mitoses. γ-H2AX foci were scored 15, 30, 60, 120 min and 24 h post irradiation. RESULTS: Our results revealed that the frequency of dicentric chromosomes in cells exposed at 37°C to gamma-rays was higher than after exposure at 0.8 and 20°C. No effect of temperature was observed on the number of γ-H2AX foci as well as on the intra- and inter-individual variations of the dicentric yield and the number of γ-H2AX foci. CONCLUSIONS: Temperature at exposure to ionizing radiation has a pronounced effect on the level of cytogenetic damage but not γ-H2AX foci.