Pollutant-adsorbed nanoplastics (PANs): the influence of physicochemical properties on biodistribution and brain toxicity following inhalation

/Abstract Plastic pollution is a critical environmental and health issue, with global plastic production reaching 390.7 million metric tons in 2021 and climbing. Only a small fraction of plastic waste is recycled, leading to the accumulation of plastics in the environment and the unavoidable generation of microplastics and nanoplastics through various degradation pathways. Nanoplastics are particularly concerning due to their potential to enter the human body through inhalation and subsequently traffic to the brain, inducing neurotoxicity. This study aims to investigate the formation, distribution, and health impacts of pollutant-adsorbed nanoplastics (PANs), which are composite particles formed by the adsorption of airborne pollutants onto nanoplastics. Our central hypothesis is that the physicochemical properties of resulting pollutant/nanoplastic assemblies (i.e., PANs) alter the biodistribution and toxicity of the pollutants, exacerbating their harmful effects upon inhalation. To test this hypothesis, we employ advanced label-free imaging techniques to detect and characterize PANs in environmental and biological samples. The first aim is to develop and optimize label-free methodologies that do not rely on chemical isolations for detecting and quantifying PANs collected in various environments. This includes employing advanced detection techniques such as enhanced dark field/hyperspectral imaging (EDF/HSI) and Raman spectroscopy to analyze size-segregated PANs captured from major roadways, agricultural fields, and industrially adjacent ocean spray. These analyses will inform synthesis of contrived PANs in a controllable fashion. Achieving this aim will establish optimized detection techniques and generate fundamental data on PAN concentrations in real-world environments. The second aim focuses on investigating the biodistribution, accumulation, and organ-specific toxicological impacts of PANs in rodent models. Detailed analyses will be conducted to determine PAN localization and target-specific endpoints in brain tissue using techniques like mass spectrometry imaging (MSI) and transcriptomics. The expected outcomes include a detailed understanding of how PANs travel within the body and their specific impacts on the brain, and how this depends on the specific combinations of pollutants and nanoplastics. We will investigate ubiquitous airborne nanoplastics (e.g., PE, PVC) and pollutants with known neurotoxicity (e.g., mercury, lead, diazinon, chlorpyrifos). The third aim seeks to elucidate the mechanisms by which PANs interact with and traverse the blood-brain barrier (BBB) to yield neurotoxic effects. The proposed research challenges the traditional paradigm of studying nanoplastics and pollutants as isolated entities by investigating their combined effects. By elucidating the mechanisms of PAN transport and their toxicological impacts, this study aims to provide crucial insights into the health risks posed by PANs and inform public health guidelines and regulatory policies. The findings will contribute to the development of effective strategies to mitigate the health risks associated with pollutants and nanoplastics, advancing the fields of human health and toxicology. Project Number: 1R01ES037331-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Environmental Health Sciences (NIEHS) | Principal Investigator: Randy Carney (+1 co-PI) | Institution: UNIVERSITY OF CALIFORNIA AT DAVIS, DAVIS, CA | Award Amount: $765,348 | Activity Code: R01 | Study Section: Neurotoxicology and Alcohol Study Section[NAL] View on NIH RePORTER: https://reporter.nih.gov/project-details/11297377