Effect of dopamine-functionalization, charge and pH on protein corona formation around TiO2 nanoparticles

by P. Siani and C. Di Valentin
Nanoscale 2022, 14, pp 5121 View at Publisher
DOI: 10.1039/D1NR07647G


Inorganic nanoparticles (NPs) are gaining increasing attention in nanomedicine because of their stimuli responsiveness, which allows combining therapy with diagnosis. However, little information is known about their interaction with intracellular or plasma proteins when they are introduced in a biological environment. Here we present atomistic molecular dynamics (MD) simulations investigating the case study of dopamine-functionalized TiOnanoparticles and two proteins that are overexpressed in cancer cells, i.e. PARP1 and HSP90, since experiments proved them to be the main components of the corona in cell cultures. The mechanism and the nature of the interaction (electrostatic, van der Waals, H-bonds, etc.) is unravelled by defining the protein residues that are more frequently in contact with the NPs, the extent of contact surface area and the variations in the protein secondary structures, at different pH and ionic strength conditions of the solution where they are immersed to simulate a realistic biological environment. The effects of the NP surface functionalization and charge are also considered. Our MD results suggest that less acidic intracellular pH conditions in the presence of cytosolic ionic strength enhance PARP1 interaction with the nanoparticle, whereas the HSP90 contribution is partly weakened, providing a rational explanation to existing experimental observations.