Tuning in Vivo Transport of Organic Dyes by Renal‐Clearable Gold Nanoparticles for Prolonged Kidney Imaging and Reporting Unilateral Kidney Injuries

The detection of unilateral kidney injury remains challenging owing to the intrinsic compensatory mechanism of the kidneys. Noninvasive kidney imaging using renal-clearable near-infrared (NIR) agents has shown promise in evaluating renal function. To enable accurate detection of unilateral kidney injury, herein, we developed a high-contrast NIR imaging agent of 800CW-Au by conjugating IRDye800CW with renal-clearable gold nanoparticles (Au₂₅SG₁₈). Compared with free IRDye800CW, the pharmacokinetics of the dye was significantly tailored after conjugation on Au₂₅SG₁₈, resulting in enhanced blood retention, reduced vascular extravasation, and lower affinity with background tissue. Consequently, 800CW-Au achieved noninvasive kidney imaging with contrast enhancement > 100% for up to 12 h, much longer than the previously reported zwitterionic ZW800-1 (∼10 min) and PEGylated IRDye800CW (∼4 min). We then established two representative mouse models of unilateral kidney injuries, including unilateral ureteral obstruction and ischemia-reperfusion injury. According to its kinetics of renal enhancement and derived parameters, 800CW-Au sensitively detected the functional impairment in the injured kidney and the compensatory hyperfiltration in the contralateral kidney, which the conventional blood biomarkers and global glomerular filtration rate were all insensitive to detect. This strategy of our work will provide guidance for developing renal NIR agents and advance the noninvasive detection of unilateral kidney injury.