Pathology-Responsive Nanoprobes for NIR-II Imaging of Acute Kidney Injury.

Acute kidney injury (AKI), a prevalent life-threatening syndrome triggered by drug-induced nephrotoxicity, ischemia-reperfusion injury (IRI), and surgical complications, rapidly progresses to chronic kidney disease without early intervention, escalating morbidity, and mortality. In this study, we synthesized a fluorescent probe CH-4T and leveraged disease-induced remodeling of the renal nano-bio interface during AKI to engineer a series of pathology-responsive nanoprobes (CH-4T@NP1-4). Systematic screening identified CH-4T@NP3 as optimal, exhibiting superior optical performance, stability, biocompatibility, and pathology-responsive renal accumulation. In cisplatin-AKI and IRI models, CH-4T@NP3 enabled high-sensitivity, real-time NIR-II imaging, with fluorescence signals quantitatively correlating to serum creatinine (Scr), blood urea nitrogen, kidney injury molecule-1 (KIM-1), histopathology (H&E, TUNEL), and injury severity. It dynamically monitored N-acetylcysteine (NAC) therapy, aligning with renal recovery and reducing apoptosis with enhanced penetration and signal-to-noise ratio, offering a noninvasive platform for early AKI diagnosis, severity assessment, and therapeutic evaluation.