Microplastic induced cascades of multiple cell death pathways: inflammation, immune imbalance, and cancer...

Microplastic and nanoplastic (M/NP) pollution has evolved from an environmental issue into a pressing threat to human health, with accumulating evidence showing that residue levels in human tissues are rising annually. Beyond their widespread distribution, the toxicity of these particles is critically determined by their physicochemical properties, particularly particle size, specific surface area, and polymer type. Notably, nanoplastics exhibit a high potential for crossing biological barriers, and their formation of biocoronas significantly alters their biological identity and interaction with host cells. This review systematically outlines the physiopathological pathways by which M/NPs damage the human body. We elucidate how M/NPs, following internalization via endocytosis, trigger excessive reactive oxygen species (ROS) generation, leading to organelle stress, genotoxicity, and potential nuclear entry. Crucially, we discuss the cascade network of multiple regulated cell death modalities, including apoptosis, ferroptosis, pyroptosis, and autophagy, as interconnected drivers of tissue injury. Furthermore, we explore the progression from chronic immune activation to immune exhaustion, highlighting how these dysregulated inflammatory responses remodel the tissue microenvironment and potentially promote cancer susceptibility. By synthesizing these mechanisms, this study aims to persuade the reader of the severe health risks posed by M/NPs and provides a theoretical foundation for future mechanistic investigations and human health risk assessments, rather than merely offering strategies for pollution control.