Microplastics and Nanoplastics in Health Concerning Cellular Toxicity Mechanisms, Exposure Pathways, and Global Mitigation Strategies

Microplastics (MPs) and nanoplastics (NPs) have emerged as ubiquitous environmental contaminants that pose significant threats to human health, with multiple exposure pathways (e.g., ingestion and inhalation) contributing to systemic exposure. Although growing evidence highlights their biological effects, the underlying mechanisms by which these particles induce cellular dysfunction remain incompletely understood. This review synthesizes current knowledge on the MPs/NPs-induced cellular toxicity mechanisms, including investigations into cellular uptake pathways, disruption of molecular signaling, oxidative stress, inflammatory responses, and genotoxic effects. MPs/NPs contamination can arise from consumer products and clinical procedures, with estimated Daily Microplastic Emission (DME)-based national totals (India) ranging from ~0.36 to 74 billion particles/day across oral-care product categories. At the cellular level, MPs and NPs trigger interconnected toxicological cascades, including impaired endocytosis, mitochondrial dysfunction, chronic inflammation, genotoxicity, endoplasmic reticulum (ER) stress, and accelerated cellular senescence. These mechanisms act in concert to compromise epithelial barrier integrity. Overall, MPs/NPs present substantial risks to health through multiple interconnected pathways. Local and systemic effects are plausible across exposed tissues which may also serve as a gateway for systemic distribution by these contaminants. These findings highlight the urgent need for coordinated global efforts, including restrictions on intentionally added MPs, improvements in product design, development of advanced removal technologies, and implementation of clinical prevention strategies.