Nanomaterial properties differ from those bulk materials of the same composition, allowing them to execute novel activities. A possible downside of these capabilities is harmful interactions with biological systems, with the potential to generate toxicity. An approach to assess the safety of nanomaterials is urgently required. We compared the cellular effects of ambient
ultrafine particles with manufactured
titanium dioxide (TiO2),
carbon black, fullerol, and
polystyrene (PS) nanoparticles (NPs). The study was conducted in a phagocytic cell line (RAW 264.7) that is representative of a lung target for NPs. Physicochemical characterization of the NPs showed a dramatic change in their state of aggregation, dispersibility, and charge during transfer from a buffered aqueous
solution to cell culture medium. Particles differed with respect to cellular uptake, subcellular localization, and ability to catalyze the production of
reactive oxygen species (ROS) under biotic and abiotic conditions. Spontaneous ROS production was compared by using an ROS quencher (
furfuryl alcohol) as well as an
NADPH peroxidase bioelectrode platform. Among the particles tested, ambient
ultrafine particles (UFPs) and cationic PS
nanospheres were capable of inducing cellular ROS production, GSH depletion, and toxic oxidative stress. This toxicity involves mitochondrial injury through increased
calcium uptake and structural organellar damage. Although active under abiotic conditions, TiO2 and fullerol did not induce toxic oxidative stress. While increased
TNF-alpha production could be seen to accompany UFP-induced
oxidant injury, cationic PS
nanospheres induced mitochondrial damage and cell death without
inflammation. In summary, we demonstrate that ROS generation and oxidative stress are a valid test paradigm to compare NP toxicity. Although not all materials have electronic configurations or surface properties to allow spontaneous ROS generation, particle interactions with cellular components are capable of generating oxidative stress.