# Synergistic Effect of Nanoplastics and GenX on Human Serum Albumin: The Role of Protein Corona Formation and Co-Adsorption

## TL;DR

This study explores how nanoplastics and GenX together damage human serum albumin, revealing a dual mechanism involving protein corona formation and hydrophobic binding.

## Contribution

The study identifies a novel dual pathway mechanism by which nanoplastics and GenX synergistically cause structural damage to human serum albumin.

## Key findings

- Nanoplastics exacerbate GenX-induced loosening of the HSA protein backbone.
- Nanoplastics and GenX cause significant protein aggregation and reduced α-helical content in HSA.
- The binding of GenX occurs within the hydrophobic pocket of subdomain IIIA of HSA.

## Abstract

GenX, also known as hexafluoroepoxypropane dimer acid (HFPO-DA), an emerging perfluoroalkyl substance alternative, is extensively used in industrial processes and is resistant to degradation. This persistence heightens the potential for co-occurrence and combined toxicity with other environmental pollutants. Nanoplastics (NPs), ubiquitous environmental contaminants, can exacerbate the biological toxicity of GenX. However, the molecular mechanisms by which NPs influence GenX-induced structural damage to human serum albumin (HSA) remain unclear. This study, therefore, employed multi-spectroscopic techniques, characterization assays, and molecular simulations to investigate these mechanisms. A critical limitation is that the observed structural damage occurred at a GenX concentration of 0.05–0.1 mM. The results indicate that the presence of NPs exacerbated the loosening of the protein backbone and caused a more pronounced reduction in α-helical content (NPs@GenX: 37.3%; GenX alone: 41.5%). The binding is predicted to occur within the hydrophobic pocket of subdomain IIIA of HSA. Characterization assays further revealed significant protein aggregation in systems containing NPs. The study concludes that NPs adsorb HSA through the formation of a protein corona, while simultaneously binding GenX via hydrophobic interactions. This dual pathway—direct binding of HSA to GenX and an active surface-mediated perturbation by NPs—constitutes the primary mechanism leading to aggravated structural changes. Overall, this work elucidates the molecular mechanisms by which NPs exacerbate HSA denaturation in the presence of GenX, offering valuable insights for assessing the combined ecological risks of emerging and persistent environmental pollutants.