• • uNP-CH1055 exhibits a hydrodynamic diameter of 3.3 nm, below the ~6 nm renal clearance threshold, enabling rapid urinary excretion and minimal reticuloendothelial system retention; this size control is critical for reducing long-term toxicity and facilitating clinical translation.
• • The probe operates under a 1200 nm long-pass filter, achieving low-background NIR-II imaging with high signal-to-noise ratios; this spectral window minimizes tissue autofluorescence and scattering, permitting non-invasive detection of deep renal tissue.
• • In three mechanistically distinct kidney injury models (cisplatin-induced AKI, ischemia–reperfusion injury, and unilateral ureteral obstruction), renal fluorescence intensity increased proportionally with injury severity and correlated with blood urea nitrogen, serum creatinine, KIM-1, and TUNEL readouts, demonstrating etiology-independent diagnostic capability.
• • The nanoprobe demonstrated favorable biocompatibility in cellular and animal studies, with no observed acute toxicity; this safety profile supports its potential for repeated administration in longitudinal monitoring of kidney injury progression and recovery.