Biotransformation of nanoplastics in human plasma and their permeation through a model in vitro blood-brain barrier: An in-depth quantitative analysis

Challenges in characterizing and quantifying nanoplastics within the human body hinder understanding of their transport, biotransformation, and potential for cellular penetration and barrier crossing. By implementing an innovative analytical workflow, including incorporation of gadolinium (Gd) as a tracer into the polymer matrix of nanoplastics, the fate of nanoplastics relative to an in vitro blood-brain barrier (BBB) model is elucidated in the absence or presence of a biomomolecule corona. The nanoplastics were incubated in human plasma for 5 min, 1 h, 6 h, and 24 h, after which the absorbed proteins and lipids (biocorona) were determined. A total of 268 proteins were identified in the biological coronas on polystyrene (PS) and polyvinyl chloride (PVC) nanoplastics, with the initial compositions being broadly similar on both PS and PVC. Both nanoplastics exhibited a strong affinity for phosphatidylcholines (PC) and lysophosphocholines (LPC) from human plasma. The inherent chemical composition of the nanoplastics plays a pivotal role in the corona’s evolution over time. Human induced pluripotent stem cell (iPSC)-derived endothelial cells (iECs) and astrocytes were exposed for 2 h to 5 µg L⁻¹ of pristine nanoplastics or nanoplastics covered with a biological corona (following incubation in plasma for 6 h). A relatively low concentration of PS and PVC nanoplastics was determined to be present within the cellular layer of the BBB. The number of PVC nanoplastics crossing the BBB was higher than the number of PS nanoplastics. The presence of a biological corona on these particles decreases their uptake and transcytosis. This understanding might further the development of preventive measures or therapeutic strategies to counteract potential nanoplastic-induced neurotoxicity, and provide a foundation for development of in silico models to predict the neurotoxic implications of nanoplastics.