In the present study,
UV-induced membrane destabilization by TiO2 (anatase) nanoparticles
was investigated by neutron reflectometry
(NR), small-angle X-ray scattering (SAXS), quartz crystal microbalance
with dissipation (QCM-D), dynamic light scattering (DLS), and ζ-potential
measurements for phospholipid bilayers formed by zwitterionic palmitoyloleoylphosphatidylcholine
(POPC) containing biologically relevant polyunsaturations. TiO2 nanoparticles displayed pH-dependent binding to such bilayers.
Nanoparticle binding alone, however, has virtually no destabilizing
effects on the lipid bilayers. In contrast, UV illumination in the
presence of TiO2 nanoparticles activates membrane destabilization
as a result of lipid oxidation caused by the generation of reactive
oxygen species (ROS), primarily •OH radicals. Despite
the short diffusion length characterizing these, the direct bilayer
attachment of TiO2 nanoparticles was demonstrated to not
be a sufficient criterion for an efficient UV-induced oxidation of
bilayer lipids, the latter also depending on ROS generation in bulk
solution. From SAXS and NR, minor structural changes were seen when
TiO2 was added in the absence of UV exposure, or on UV
exposure in the absence of TiO2 nanoparticles. In contrast,
UV exposure in the presence of TiO2 nanoparticles caused
large-scale structural transformations, especially at high ionic strength,
including gradual bilayer thinning, lateral phase separation, increases
in hydration, lipid removal, and potential solubilization into aggregates.
Taken together, the results demonstrate that nanoparticle–membrane
interactions ROS generation at different solution conditions act in
concert to induce lipid membrane destabilization on UV exposure and
that both of these need to be considered for understanding the performance
of UV-triggered TiO2 nanoparticles in nanomedicine.