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.