Disruption of the programmed cell death nexus: potential roles of microplastics and nanoplastics in tumorigenesis

As global plastic pollution continues to intensify, microplastics and nanoplastics (MPs/NPs) have become widely distributed in air, water, the food chain, and even the human body, constituting a novel environmental exposure that is difficult to avoid. Although there is still insufficient evidence to classify MPs/NPs as established human carcinogens, a growing body of research suggests that they may participate in tumor initiation and progression through multiple pathways, including the intrinsic toxicity of the particles themselves, pollutant carrier effects, and microenvironmental remodeling. MPs/NPs can not only enter the human body through ingestion and inhalation and achieve multi-organ distribution, but can also serve as delivery platforms for polycyclic aromatic hydrocarbons, heavy metals, and plastic additives, thereby producing a “Trojan horse” effect that amplifies the toxicity of combined exposures. This review summarizes current progress in research linking MPs/NPs to cancer, with a particular focus on their role in disrupting the cell death network. Through shared upstream events such as oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and inflammasome activation, MPs/NPs may disturb the dynamic balance among apoptosis, ferroptosis, pyroptosis, necroptosis, and cuproptosis, as well as autophagy-related stress responses, thereby exerting effects during tumor initiation, tumor microenvironment formation, tumor progression, and therapeutic resistance. We therefore present the cell death network as a hypothesis framework, and identify major methodological limitations. Future studies integrating standardized exposure assessment, systems biology, and prospective research are needed to further elucidate the key mechanisms through which MPs/NPs promote tumorigenesis via perturbation of the cell death network and to provide a theoretical basis for related health risk assessment and intervention strategies.