Polystyrene micro- and nanoplastics impair tissue regeneration and neurodevelopment in a size-dependent manner in the planarian Schmidtea mediterranea.

Micro- and nanoplastics (MNPs) enter aquatic systems as a result of massive plastic production, consumer use and inadequate waste management, interacting with the inhabiting organisms. Effective policy making requires robust hazard and risk assessment frameworks; however, current approaches rarely include the physicochemical properties of MNPs in a systematic manner, limiting the ability to identify which specific characteristics drive toxicity. In addition, developing organisms, despite their expected heightened sensitivity, remain largely overlooked in such assessments. In this study, we used the benthic organism Schmidtea mediterranea, known for its exceptional regenerative capacity, to investigate size-dependent effects on tissue development. To enable a controlled and mechanistic assessment, we deliberately selected commercially available pristine polystyrene spherical particles, allowing particle size (50 nm, 200 nm, 01 µm, and 02 µm) to serve as the primary varying parameter. All particles had a spherical structure, although the 02 µm spheres showed a rougher surface morphology characterized by the presence of associated ∼110-120 nm surface features. Particles of all size classes were internalized via either the intestine or the epidermis, accumulating predominantly within the outer epidermal layers in close proximity to the subepidermal nerve net. During regeneration, particles were detected within newly formed tissues, closely associated with the ventral nerve cords and cephalic ganglia. Consistent with these observations, our results indicate that neurodevelopmental processes emerge as particularly sensitive targets of MNP exposure. We identified clear size-specific toxicity profiles: smaller particles (50 and 200 nm) alter tyrosine hydroxylase (Smed-th) expression, indicating effects on dopaminergic neurons, whereas larger particles (01 and 02 µm) induce pronounced epidermal irritation, triggering systemic responses and broader neurotoxicity. Together, our findings establish a direct connection between particle size, uptake, and functional neurodevelopmental outcomes, advancing a more mechanistic understanding of MNP toxicity. They further underscore the necessity of integrating physicochemical particle characterization and developmental stages into hazard assessment frameworks, and highlight the importance of benthic organisms for capturing ecologically relevant exposure scenarios.