Francesca Cirillo, Fiorenza Gianì, V. Sergi, Domenica Scordamaglia, Sebastiano Giallongo, Daniele Tibullo, Giovanni Li Volti, Marcello Maggiolini, Roberta Malaguarnera, Rosamaria Lappano, Ernestina Marianna De Francesco
Micro- and nano-plastics (MNPs) are small plastic particles generated from the fragmentation of larger plastic products, which are widely manufactured and often improperly discarded. Because MNPs are not fully degradable, they persist and accumulate across all ecosystems, contributing to global environmental concerns. The detection of MNPs within the food chain and in various human tissues and biological samples has raised pressing questions about their potential health risks. Cellular exposure to MNPs induces molecular, metabolic, and biological changes that may culminate in pathological outcomes. Given the chronic, lifelong exposure to escalating doses of MNPs, their involvement in the initiation and progression of human cancers is increasingly suspected. Clinical and experimental studies support this hypothesis, although clear causal evidence is still lacking. To address this gap, research in recent years has expanded rapidly, generating a growing body of literature on MNPs and cancer. In this review, we provide an up-to-date and critical overview of the data linking MNPs exposure to human cancer. We analyze the molecular and biological mechanisms potentially underlying MNP-induced carcinogenesis, with emphasis on the main routes of human exposure and tissue-specific effects. Particular attention is given to neoplastic conditions arising in primary contact sites (gastrointestinal tract, lung, and skin) and secondary targets (liver, kidney, brain). Finally, we highlight key knowledge gaps and propose future research directions to advance this emerging field. Based on the oncogenic potential of MNPs, an exhaustive and stringent scrutiny of the most recent findings will help scientists drawing solid conclusions in this highly debated area. • Micro- and nano-plastics (MNPs) are emergent hazardous materials for human health • MNPs bioaccumulate in human cells and tissues and perturbate cell homeostasis • MNPs induce oxidative stress, DNA damage, inflammation and metabolic impairment • MNPs may trigger tumorigenic responses in tissues associated with human contact • Further studies are required to define the hazard risk associated to oncogenic MNPs