Gel-dispersed micro- and nano- polystyrene (PS), polyethylene terephthalate (PET) and polypropylene (PP) impact metabolic parameters in egg-box liver spheroid model.

Micro- and nanoplastics (MNPs) represent an emerging class of contaminants, yet their biological impacts remain poorly understood. Mechanistic research comparing polymers such as polypropylene (PP) and polyethylene terephthalate (PET) is challenging because of strong differences in hydrophobicity, buoyancy or sedimentation behavior, size distribution (aggregation) and lack of strong acute cytotoxic effects. This study introduces an innovative in vitro dosing platform with 3D hepatic spheroids, providing a dosimetrically robust model to investigate metabolic and bioenergetic effects of chronic MNP exposure. Gel encapsulation was used to expose spheroids for up to 21 days to MNPs of different composition and size. MNPs accumulated in spheroids with polymer-specific localization. Cytotoxicity was limited, but metabolic profiling revealed consistent bioenergetic shifts. This work highlights the importance of particle size distributions and introduces alginate bead encapsulation as a reproducible dosing strategy for comparing MNPs and defining toxic doses linked to biologically relevant molecular and cellular events.