Malekkhaiat Häffner S, Parra-Ortiz E, Skoda M W A, Saerbeck T, Browning K L, Malmsten M
Department of Pharmacy, University of Copenhagen, DK-2100 Copenhagen, Denmark.
Department of Pharmacy, University of Copenhagen, DK-2100 Copenhagen, Denmark.
J Colloid Interface Sci. 2021 Feb 15;584:19-33. doi: 10.1016/j.jcis.2020.09.046. Epub 2020 Sep 22.
Membrane interactions and photooxidative membrane destabilization of titanium dioxide (TiO) nanoparticles were investigated, focusing on the effects of membrane composition, notably phospholipid headgroup charge and presence of cholesterol. For this, we employed a battery of state-of-the-art methods for studies of bilayers formed by zwitterionic palmitoyloleoylphosphatidylcholine (POPC) containing also polyunsaturated palmitoylarachidonoylphosphocholine (PAPC), as well as its mixtures with anionic palmitoyloleoylphosphatidylglycerol (POPG) and cholesterol. It was found that the TiO nanoparticles display close to zero charge at pH 7.4, resulting in aggregation. At pH 3.4, in contrast, the 6 nm TiO nanoparticles are well dispersed due to a strongly positive ζ-potential. Mirroring this pH dependence, TiO nanoparticles were observed to bind to negatively charged lipid bilayers at pH 3.4, but much less so at pH 7.4. While nanoparticle binding has some destabilizing effect alone, illumination with ultraviolet (UV) light accentuates membrane destabilization, a result of oxidative stress caused by generated reactive oxygen species (ROS). Neutron reflectivity (NR), quartz crystal microbalance (QCM), and small-angle X-ray scattering (SAXS) results all demonstrate that membrane composition strongly influences membrane interactions and photooxidative destabilization of lipid bilayers. In particular, the presence of anionic POPG makes the bilayers more sensitive to oxidative destabilization, whereas a stabilizing effect was observed in the presence of cholesterol. Also, structural aspects of peroxidation were found to depend strongly on membrane composition, notably the presence of anionic phospholipids. The results show that membrane interactions and UV-induced ROS generation act in concert and need to be considered together to understand effects of lipid membrane composition on UV-triggered oxidative destabilization by TiO nanoparticles, e.g., in the context of oxidative damage of bacteria and cells.
研究了二氧化钛（TiO₂）纳米颗粒的膜相互作用和光氧化膜去稳定作用，重点关注膜组成的影响，特别是磷脂头部基团电荷和胆固醇的存在。为此，我们采用了一系列先进方法来研究由两性离子棕榈酰油酰磷脂酰胆碱（POPC）形成的双层膜，其中还含有多不饱和棕榈酰花生四烯酰磷脂酰胆碱（PAPC），以及它与阴离子棕榈酰油酰磷脂酰甘油（POPG）和胆固醇的混合物。研究发现，TiO₂纳米颗粒在pH 7.4时电荷接近零，导致聚集。相比之下，在pH 3.4时，6纳米的TiO₂纳米颗粒由于具有强正ζ电位而得到良好分散。与这种pH依赖性相对应，观察到TiO₂纳米颗粒在pH 3.4时与带负电荷的脂质双层结合，但在pH 7.4时结合程度要小得多。虽然纳米颗粒结合本身有一定的去稳定作用，但用紫外线（UV）照射会加剧膜的去稳定，这是由产生的活性氧（ROS）引起的氧化应激的结果。中子反射率（NR）、石英晶体微天平（QCM）和小角X射线散射（SAXS）结果均表明，膜组成强烈影响脂质双层的膜相互作用和光氧化去稳定作用。特别是，阴离子POPG的存在使双层膜对氧化去稳定更敏感，而在胆固醇存在时则观察到稳定作用。此外，过氧化的结构方面也强烈依赖于膜组成，特别是阴离子磷脂的存在。结果表明，膜相互作用和UV诱导的ROS产生协同作用，需要综合考虑才能理解脂质膜组成对TiO₂纳米颗粒引发的UV触发氧化去稳定作用的影响，例如在细菌和细胞氧化损伤的背景下。
