Different toxicity of anatase and rutile TiO2 nanoparticles on macrophages: Involvement of difference in affinity to proteins and phospholipids

TiO 2 nanoparticles (NPs) are well-known nanomaterials (NMs), widely used in cosmetics, solar cells, photo-catalysts and additives. Anatase and rutile are the two main crystalline phases of TiO 2 NPs and have distinct electrical and optical properties. However, their relative toxicity to organisms is a current topic of debate. In this study, we synthesize both anatase NPs (TiO 2 -A) and rutile NPs (TiO 2 -R) with similar particle sizes (20–40   nm), surface areas (51–52   m 2 /g) and Zeta potentials (−13.4 to −13.7   mV), and investigate their toxicity to macrophages. Contrary to previous findings, TiO 2 -A show a lower percentage cell deaths compared to TiO 2 -R (10% vs 20% at 50   mg/L), indicating a lower toxicity compared to TiO 2 -R. The macrophages treated with TiO 2 -A and TiO 2 -R have similar levels of reactive oxygen species (ROS) and the autophagy marker LC3, implying that our observed difference in toxicity is not attributed to oxidative damage and autophagy. Interestingly, TiO 2 -A cause less severe necrosis and lysosomal membrane permeabilization (LMP), but more severe mitochondrial dysfunction. Adsorption assays further reveal that TiO 2 -A and TiO 2 -R have a higher affinity to proteins and phospholipids, respectively. This study demonstrates an important role of crystal phase-related surface affinity to different biomolecules in nanotoxicity.