Bidirectional interplay in the digestive microenvironment: Nanoplastics-mediated enzyme impairment modulates bisphenol analogs desorption.

With the widespread application of food-grade plastic products, bisphenol analogs (BPs) as plastic additives have attracted increasing attention, particularly in the presence of nanoplastics (NPl) generated from plastic degradation. This study investigated the impact of NPl on the digestive fate of various BPs, emphasizing the interplay among BPs, NPl, and digestive enzymes. Our findings revealed that the cumulative release of four BPs loaded onto NPl followed the order: bisphenol F (BPF) > bisphenol A (BPA) > bisphenol B (BPB) > bisphenol AF (BPAF), highlighting their distinct desorption behaviors under simulated digestive conditions. Digestive enzymes actively mediated BPs desorption from NPl through competitive adsorption and enhanced solubilization. Among these, pepsin is the most significantly affected by BPs-loaded NPl exposure. While pepsin facilitated BPs release, BPs-loaded NPl concurrently inhibited pepsin activity, with inhibition rates reaching up to 77%. Molecular analyses revealed that NPl promoted BPs association near the active site of pepsin and induced secondary structural perturbations characterized by increased β-sheet enrichment and reduced conformational flexibility. These alterations diminished pepsin-mediated desorption, establishing a bidirectional interplay that modulates the digestive fate of BPs. Overall, this study provides insights into the coupled interactions between BPs migration and digestive enzyme perturbation at the nano-bio interface.