The micro- and nanoplastics exposome feedback loop drives synergistic air–lung toxicity

Airborne micro- and nanoplastics (MNPs) are now recognized as persistent components of the atmospheric exposome. While their presence is established, their toxicological role remains incompletely understood. In this perspective, we propose the MNP Exposome Feedback Loop-a hypothesized self-reinforcing system in which MNPs act not as passive pollutants, but as active vectors and catalytic amplifiers of airborne toxicity. We map emerging scientific insights to explore how atmospherically aged MNPs, through adsorption of pollutants and development of biofilms, form hybrid complexes with particulate matter (PM). Upon inhalation, these complexes are posited to trigger synergistic oxidative stress, epithelial barrier breakdown, and chronic inflammation, thereby potentially compounding susceptibility to respiratory diseases. We argue that the critical risk lies not in additive effects, but in this synergistic amplification. To preemptively address this potential risk, we introduce two forward-looking frameworks: (1) an Exposome-AI Framework for predictive toxicology, integrating atmospheric simulation, multi-omics, and machine learning; and (2) a new regulatory category, Vectorial Particulate Matter (VPM), defined by a particle's dynamic capacity to transport and amplify harm. This perspective aims to reframe MNPs as potential catalytic agents within a coupled atmosphere-lung system and to set a pathway for translating mechanistic insight into preventive regulation.