Systemic histopathological responses to nanoplastic exposure: a review of cellular toxicity and organ-level pathology in mammalian systems

Nanoplastics (NPs), a subfraction of microplastics smaller than 1 μm, are increasingly recognized for their ability to cross biological barriers and induce organ-level toxicity; however, their systemic histopathological effects remain fragmented across individual studies. This review summarizes current in vivo mammalian evidence on NP-induced cellular toxicity and organ-specific histopathological changes based on a structured literature search of PubMed, Scopus, and Web of Science covering studies published between 2000 and 2024. The findings were narratively organized by organ system. Across the nervous, respiratory, gastrointestinal, hepatobiliary/renal, and reproductive systems, NPs consistently induce common pathological signatures, including immune cell infiltration, apoptosis, fibrosis, epithelial barrier disruption, and ultrastructural organelle damage. These lesions indicate conserved mechanisms involving oxidative stress, inflammatory signaling, impaired cellular homeostasis, and organ–organ crosstalk, such as gut–liver and hepato–renal interactions, which may amplify systemic toxicity. Collectively, the evidence demonstrates that nanoplastics act as system-wide toxicants capable of multi-organ histopathological disruption, distinct from larger microplastics or other nanoparticles, underscoring the need for further mechanistic and pathology-driven evaluation.