Abstract：
Renal clearable nanoparticles have been drawing much attention as they can avoid prolonged accumulation in the body by efficiently clearing through the kidneys. While much effort has been made to understand their interactions within the kidneys, it remains unclear whether their transport could be influenced by other organs, such as the liver, which plays a crucial role in metabolizing and eliminating both endogenous and exogenous substances through various biotransformation processes. Here, by utilizing renal clearable IRDye800CW conjugated gold nanocluster (800CW4-GS18-Au25) as a model, we found that although 800CW4-GS18-Au25 strongly resisted serum-protein binding and exhibited minimal accumulation in the liver, its surface was still gradually modified by hepatic glutathione-mediated biotransformation when passing through the liver, resulting in the dissociation of IRDye800CW from Au25 and biotransformation-generated fingerprint message of 800CW4-GS18-Au25 in urine, which allowed us to facilely quantify its urinary biotransformation index (UBI) via urine chromatography analysis. Moreover, we observed the linear correlation between UBI and hepatic glutathione concentration, offering us a noninvasive method for quantitative detection of liver glutathione level through a simple urine test. Our discoveries would broaden the fundamental understanding of in vivo transport of nanoparticles and advance the development of urinary probes for noninvasive biodetection.
摘要：
肾脏可清除的纳米颗粒已经引起了很多关注，因为它们可以通过有效地清除肾脏来避免在体内的长期积累。虽然已经做出了很多努力来了解它们在肾脏内的相互作用，尚不清楚它们的运输是否会受到其他器官的影响，比如肝脏，它在通过各种生物转化过程代谢和消除内源性和外源性物质中起着至关重要的作用。这里,通过利用肾透明IRDye800CW共轭金纳米簇（800CW4-GS18-Au25）作为模型，我们发现，尽管800CW4-GS18-Au25强烈抵抗血清蛋白结合，并在肝脏中表现出最小的积累，通过肝脏时，其表面仍被肝谷胱甘肽介导的生物转化逐渐修饰，导致IRDye800CW从Au25中解离，并在尿液中生物转化产生800CW4-GS18-Au25的指纹信息，这使我们能够通过尿液色谱分析轻松量化其尿液生物转化指数（UBI）。此外，我们观察到UBI和肝谷胱甘肽浓度之间的线性相关性，为我们提供了一种通过简单的尿液测试定量检测肝脏谷胱甘肽水平的非侵入性方法。我们的发现将扩大对纳米颗粒体内运输的基本理解，并促进用于非侵入性生物检测的尿液探针的开发。
