Abstract
Secondary nanoplastics (NPs) caused by degradation and aging due to environmental factors are the main source of human exposure, and alterations in the physicochemical and biological properties of NPs induced by environmental factors cannot be overlooked. In this study, pristine polystyrene (PS) NPs to obtain ultraviolet (UV)-aged PS NPs (aPS NPs) as secondary NPs is artificially aged. In a mouse oral exposure model, the nephrotoxicity of PS NPs and aPS NPs is compared, and the results showed that aPS NPs exposure induced more serious destruction of kidney tissue structure and function, along with characteristic changes in ferroptosis. Subsequent in vitro experiments revealed that aPS NPs-induced cell death in human renal tubular epithelial cells involved ferroptosis, which is supported by the use of ferrostatin-1, a ferroptosis inhibitor. Notably, it is discovered that aPS NPs can enhance the binding of serum transferrin (TF) to its receptor on the cell membrane by forming an aPS-TF complex, leading to an increase in intracellular Fe2+ and then exacerbation of oxidative stress and lipid peroxidation, which render cells more sensitive to ferroptosis. These findings indicated that UV irradiation can alter the physicochemical and biological properties of NPs, enhancing their kidney biological toxicity risk by inducing ferroptosis.