Microplastics and nanoplastics in human toxicity: ROS-mediated mechanisms, cellular damage and systemic effects

Microplastics (MPs, less than 5 mm) and nanoplastics (NPs, less than 1 μm) have become widespread environmental contaminants with significant implications for human health. Owing to their small size, large surface area, and physicochemical reactivity, MPs and NPs readily interact with biological membranes, promote cellular uptake, and accumulate within organelles such as mitochondria, lysosomes, and the endoplasmic reticulum. ROS overproduction disrupts mitochondrial dynamics, induces DNA damage, alters lipid metabolism, and affects redox-sensitive signalling pathways, including MAPK, PI3K/Akt, NF-κB, p53, and TGF-β. These molecular events collectively initiate apoptosis, autophagy, inflammation, and genotoxicity. At the systemic level, experimental MP and NP exposure has been associated with hepatotoxicity, nephrotoxicity, cardiopulmonary injury, reproductive impairment, neurotoxicity, gut microbiome dysbiosis, endocrine disruption, and elevated cancer risk. Furthermore, MPs and NPs can act as vectors of co-contaminants, increasing the bioavailability and toxicity of associated pollutants such as plasticizers and heavy metals. This review consolidates current understanding of the sources, cellular uptake, ROS-mediated mechanisms, and multi-organ toxicological effects of MPs and NPs.