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A fundamental understanding of how these nanoparticles accumulate in diseased kidneys at the cellular level is essential to enhance their effectiveness and minimize side effects on adjacent healthy tissues. Herein, we report that the accumulation of glutathione\u2010coated, near\u2010infrared emitting gold nanoparticles (GS\u2010AuNPs) correlates strongly with the necrotic stages of injured proximal tubular cells. Using a rhabdomyolysis\u2010induced acute kidney injury (AKI) mouse model, we observed that GS\u2010AuNPs were significantly accumulated in the extracellular lumen of proximal tubular epithelial cells (PTECs) at advanced necrotic stage, where cellular debris and released intracellular contents impeded their clearance. In contrast, during early necrosis, GS\u2010AuNPs were still cleared through the unobstructed lumen. Additionally, intracellular uptake of GS\u2010AuNPs was significantly reduced across all necrotic stages. These findings underscore the need for new strategies to design nanoparticles that can effectively target and be taken up by the diseased tubular cells before extensive necrosis occurs; so that nanoparticle\u2010mediated drug delivery for kidney disease treatment can be achieved with desired efficacy and precision.<\/jats:p>","DOI":"10.1002\/anie.202417024","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T15:40:08Z","timestamp":1729266008000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Nanoparticle Transport in Proximal Tubules with Rhabdomyolysis\u2010Induced Necrosis"],"prefix":"10.1002","volume":"64","author":[{"given":"Yingyu","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry The University of Texas at Dallas 800\u2005W. Campbell Rd.  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