The measurement of nanoparticles (NPs) in a biological matrix is essential in various toxicity studies. However, the current knowledge has limitations in differentiating particulate and ionic forms and further identification of their biotransformation. Herein, we evaluate the biotransformation and differential lung clearance kinetics of particulate and ionic forms using PEGylated silver NPs (AgNP-PEGs; 47.51 nm) and PEGylated gold NPs (AuNP-PEGs; 11.76 nm). At 0, 3, and 6 h and 1, 3, 7, and 14 days after a single pharyngeal aspiration in mice at 25 μg/mouse, half of the lung is digested by proteinase K (PK) to separate particulates and ions, and the other half is subjected to the acid digestion method for comparison. The quantitative and qualitative evaluation of lung clearance kinetics suggests that AgNP-PEGs are quickly dissolved and transformed into insoluble silver sulfide (Ag₂S), which shows a fast-clearing early phase (0 −6 h; particle T_1/2: 4.8 h) and slow-clearing late phase (1 −14 days; particle T_1/2: 13.20 days). In contrast, AuNP-PEGs were scarcely cleared or biotransformed in the lungs for 14 days. The lung clearance kinetics of AgNPs and biotransformation shown in this study can be informed by the PK digestion method and cannot be obtained using the acid digestion method.

生物基质中纳米粒子 (NPs) 的测量在各种毒性研究中是必不可少的。然而，目前的知识在区分颗粒和离子形式以及进一步识别它们的生物转化方面存在局限性。在此，我们使用聚乙二醇化银纳米粒子（AgNP-PEG；47.51 nm）和聚乙二醇化金纳米粒子（AuNP-PEG；11.76 nm）评估颗粒和离子形式的生物转化和微分肺清除动力学。在 0、3 和 6 小时以及 1、3、7 和 14 天后，以 25 μg/小鼠的剂量对小鼠进行单次咽部抽吸后，一半的肺被蛋白酶 K (PK) 消化以分离颗粒和离子，并且另一半用酸消解法比较。₂ S)，显示快速清除早期阶段（0 -6 小时；粒子 T _1/2：4.8 小时）和缓慢清除后期（1 -14 天；粒子 T _1/2：13.20 天）。相比之下，AuNP-PEG 在 14 天内几乎没有在肺部被清除或生物转化。本研究中显示的 AgNPs 和生物转化的肺清除动力学可以通过 PK 消化方法获知，而不能使用酸消化方法获得。