Thermodynamic and electron paramagnetic resonance descriptors of TiO₂ nanoforms interaction with plasma albumin: The...

Protein-nanomaterial interaction is a topic of great interest for nanotechnology research, particularly for advancing strategies in nanomedicine and nanosafety. This study explores the thermodynamic signatures associated with the interactions of six TiO₂ nanoforms, (differing in their crystalline structure, surface properties and particle size) with bovine serum albumin as model protein. By integrating findings from electron paramagnetic resonance spectroscopy (EPR) regarding the free radical generation following interaction, together with information on the stability and conformational changes of the protein during adsorption on TiO₂ nanomaterials, we aim to elucidate the binding mechanisms and identify the primary factors influencing nanomaterial's reactivity. The effect of the particle size, crystalline structure and surface properties on the binding parameters, protein structural stability and EPR data is discussed. Finally, the relevant parameters suitable for understanding molecular interactions at the bio/nano interface have been corroborated with the toxicological outcomes resulting from the measurements on the viability, proliferation and real time attachment of relevant cell lines, as well as with the detection of DNA strand breaks and oxidized DNA at the single-cell level. Thermodynamic and EPR parameters emerge as key descriptors for determining adsorption/binding processes and toxic effects of nanomaterials. The rankings with respect to cell damage and to oxidative stress inducing potential follow the same ranking seen in nanomaterial's influence on the BSA structural stability, binding affinity and enthalpic character of the interaction. Our findings highlight the intricate relationships between the parameters governing bio-nano interactions and the toxicity of the nanomaterials, and their significance in assessing nanomaterial safety and efficacy.