A systematic investigation into the interaction of different metal nanoparticles with human serum albumin

• Regardless of composition, all nanoparticles (Pt, Pd, Ag, Au) formed a stable, static corona with HSA, highlighting a common interaction mechanism. • Pt nanoparticles exhibit the highest HSA binding, followed by Pd, while Au and Ag showed the weakest interactions, influencing their potential biomedical applications. • The binding strength of Pd, Ag, and Au nanoparticles with HSA decreased with rising temperature, while Pt binding remained relatively stable, suggesting temperature-dependent tunability. • Enthalpy played a dominant role in nanoparticle-HSA interactions, with Gibbs free energy changes confirming spontaneous binding, and entropy shifts linked to protein conformational changes. The successful translation of nanomedicines from laboratories to clinics warrants a thorough understanding of the interaction between materials and biological matrices. This is because the surface identity of nanomaterials tends to change invariably upon exposure to either blood or serum, which is relevant for both in vivo and in vitro applications. Insights into such interactions have been previously obtained for gold nanoparticles (AuNPs) of different shapes, sizes, and surface chemistries by employing human serum albumin (HSA) as the most abundant model blood protein. The outcomes of these studies have highlighted the need to expand research into other nanoparticle systems to determine their potential in nanomedicine. Such studies can enrich our understanding of nano-bio interactions by identifying their molecular basis on various chemical surfaces. The current work focuses on understanding the role of metal composition (in NPs) in its interaction with HSA, a model blood protein. We chose citrate-capped Au, Ag, Pt, and Pd nanoparticles and studied their interactions with HSA. The study showed that the nanoparticle composition had little influence on the binding nature, as all nanoparticles showed static binding with HSA. However, interaction constants such as the quenching efficiency ( k SV ), binding constant ( k b ), degree of cooperativity ( n ), and thermodynamics were not only dependent on the nanoparticle metal core but also on the temperature at which the interaction occurred. This systematic study provides an in-depth understanding of how nanoparticles of different metallic compositions interact with HSA and identifies the key parameters that can be used to modulate this interaction, which is critical for expanding the applications of nanoparticles in nanomedicine.