Tracking the Cellular Degradation of Silver Nanoparticles: Development of a Generic Kinetic Model

Understanding the degradation of nanoparticles (NPs) after crossing the cell plasma membrane is crucial in drug delivery designs and cytotoxicity assessment. However, the key factors controlling the degradable kinetics remain unclear due to the absence of a quantification model. In this study, subcellular imaging of silver nanoparticles (AgNPs) was used to determine the intracellular transfer of AgNPs, and single particle ICP-MS was utilized to track the degradation process. A cellular kinetic model was subsequently developed to describe the uptake, transfer, and degradation behaviors of AgNPs. Our model demonstrated that the intracellular degradation efficiency of AgNPs was much higher than that determined by mimicking testing, and the degradation of NPs was highly influenced by cellular factors. Specifically, deficiencies in Ca or Zn primarily decreased the kinetic dissolution of NPs, while a Ca deficiency also resulted in the retardation of NP transfer. The biological significance of these kinetic parameters was strongly revealed. Our model indicated that the majority of internalized AgNPs dissolved, with the resulting ions being rapidly depurated. The release of Ag ions was largely dependent on the microvesicle-mediated route. By changing the coating and size of AgNPs, the model results suggested that size influenced the transfer of NPs into the degradation process, whereas coating affected the degradation kinetics. Overall, our developed model provides a valuable tool for understanding and predicting the impacts of the physicochemical properties of NPs and the ambient environment on nanotoxicity and therapeutic efficacy. © 2024 American Chemical Society.