TY - JOUR

T1 - Oxidation of Polyunsaturated Lipid Membranes by Photocatalytic Titanium Dioxide Nanoparticles

T2 - Role of pH and Salinity

AU - Parra-Ortiz, Elisa

AU - Haffner, Sara Malekkhaiat

AU - Saerbeck, Thomas

AU - Skoda, Maximilian W. A.

AU - Browning, Kathryn L.

AU - Malmsten, Martin

PY - 2020

Y1 - 2020

N2 - 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 zeta-potential measurements for phospholipid bilayers formed by zwitterionic palmitoyloleoylphos-phatidylcholine (POPC) containing biologically relevant poly unsaturations. TiO2 nanoparticles displayed pH-dependent bind ing 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)-O-center dot 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.

AB - 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 zeta-potential measurements for phospholipid bilayers formed by zwitterionic palmitoyloleoylphos-phatidylcholine (POPC) containing biologically relevant poly unsaturations. TiO2 nanoparticles displayed pH-dependent bind ing 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)-O-center dot 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.

KW - lipid membranes

KW - polyunsaturation

KW - lipid oxidation

KW - photocatalysis

KW - nanoparticles

KW - INORGANIC NANOPARTICLES

KW - ESCHERICHIA-COLI

KW - EXTRACELLULAR PH

KW - PARTICLE-SIZE

KW - ZERO CHARGE

KW - THIN-FILMS

KW - TIO2

KW - PEROXIDATION

KW - BILAYERS

KW - NANOMATERIALS

U2 - 10.1021/acsami.0c08642

DO - 10.1021/acsami.0c08642

M3 - Journal article

C2 - 32589394

VL - 12

SP - 32446

EP - 32460

JO - ACS applied materials & interfaces

JF - ACS applied materials & interfaces

SN - 1944-8244

IS - 29

ER -