Oxidation of Polyunsaturated Lipid Membranes by Photocatalytic Titanium Dioxide Nanoparticles: Role of pH and Salinity

Abstract

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.

Mesoporous silica as a matrix for photocatalytic titanium dioxide nanoparticles: lipid membrane interactions

“…Hence, photocatalytic effects of the silica-loaded TiO 2 nanoparticles are correspondingly larger and direct membrane interactions relatively less important. Taken together, these findings extend on previous mechanistic studies on oxidative destabilization of lipid membranes by photocatalytic nanoparticles 4,16,17 by outlining how photocatalytic nanoparticles can be incorporated into other nanomaterials for increased colloidal stability and yet retain their capacity for photocatalytic destabilization of lipid membranes. As such, the study provides new information on a widely employed practice in applications of photocatalytic nanomaterials, which had so far not been investigated mechanistically.…”

“…On loading the silica nanoparticles (100 ppm) with TiO 2 nanoparticles (25 ppm), increased oxidation was expectedly observed, an effect which, however, was not further accentuated on increasing the TiO 2 load to 100 ppm. As observed previously, 16 the oxidation rate monitored by C 11 -BODIPY was substantially higher at pH 7.4 than at pH 3.4, an effect possibly influenced by hydroxyl radicals converting into their less reactive conjugate base at low pH, although protonation of the superoxide radical below pH 4.8 may balance such effects. 30 At pH 7.4, the oxidation rate was found to be slightly lower for TiO 2 loaded into virus-like nanoparticles than that for either free TiO 2 or TiO 2 loaded into smooth mesoporous silica nanoparticles, although at pH 3.4, no differences between these were observed.…”

“…Thus, a rough outer layer was necessary to include to fit the experimental data (Model 2 in Scheme S1 †), as previously described by us for free TiO 2 nanoparticles. 16 As shown in Fig. 7B, the hydration of this top layer was comparable, although slightly higher, for TiO 2 nanoparticles loaded into either smooth or virus-like silica nano- particles than for free TiO 2 nanoparticles.…”

“…1B and S1 †), which was subsequently suppressed at higher pH. 16 Analogously, the virus-like mesoporous silica nanoparticles displayed some very minor aggregation at pH 5.4, but was effectively colloidally stable at pH 3.4 and 7.4. Similarly, smooth mesoporous silica nanoparticles remained well dispersed over the pH range 3.4-7.4 (Fig.…”

“…S7 and S8 †), comparable to those previously observed by us for UV exposure alone. 16,17 Therefore, the effect of the silica surface topography in the absence of TiO 2 did not show a significant effect on top of the UV effect.…”