Abstract
Microplastics and nanoplastics have become ubiquitous environmental pollutants. The threat these plastics pose to human health has fueled research focused on their pathophysiology and toxicology, yet many of their fundamental properties - for example, their in vivo pharmacokinetics - remain poorly understood. In this investigation, we have harnessed positron emission tomography (PET) to track the in vivo fate of micro- and nanoplastics administered to mice intratracheally and intravenously. To this end, 1 μm and 20 nm diameter amine-functionalized polystyrene particles were modified with an isothiocyanate-bearing variant of desferrioxamine (DFO) and radiolabeled with the positron-emitting radiometal [(89)Zr]Zr(4+). Both radioplastics - [(89)Zr]Zr-DFO-PS1000 and [(89)Zr]Zr-DFO-PS20 - were produced in ∼95% radiochemical yield and found to be >85% stable to demetallation over one week at 37 °C in human serum and simulated lung fluid. The incubation of [(89)Zr]Zr-DFO-PS1000 and [(89)Zr]Zr-DFO-PS20 with MH-S cells revealed that the majority of the former were phagocytosed by alveolar macrophages within 4 h, while the latter largely evaded consumption. Finally, the in vivo behavior of the radioplastics was interrogated in mice upon intravenous and intratracheal administration. PET imaging and biodistribution experiments revealed that the intravenously injected plastics accumulated primarily in the liver and spleen, yielding hepatic radioactivity concentrations of 101 ± 48 %ID/g and 92 ± 22 %ID/g at 168 h post-injection for [(89)Zr]Zr-DFO-PS1000 and [(89)Zr]Zr-DFO-PS20(,) respectively. In contrast, the mice that received the radioplastics via intratracheal installation displayed the highest uptake in the lungs at the end of one week: 4 ± 2 %ID/g for [(89)Zr]Zr-DFO-PS1000 and 32 ± 6 %ID/g for [(89)Zr]Zr-DFO-PS20. Ultimately, this work illustrates the critical role that the route of exposure plays in the bioaccumulation of plastic particles, reveals that size dramatically influences the pulmonary retention of inhaled particles, and underscores the value of PET imaging as a tool for studying the pharmacokinetics of environmental pollutants.