Kidney disease is usually “silent” at the early stage but can lead to severe kidney failure later on. The development of bioimaging probes with rapid distribution and long-term retention in the kidney is significant for the precise diagnosis of renal diseases. Here, a strategy for the peptide-mediated delivery and long-term accumulation (>48 h) of second near-infrared window (NIR-II) fluorophores into the kidney is demonstrated. It is shown that both the hepatic-cleared organic molecules and fast renal-cleared ultrasmall nanoparticles can be retained in the kidney after conjugation to the peptide with high polarity. Moreover, a ROS-responsive activatable bilateral NIR-II sensor was designed based on the kidney targeting peptide, which enables both in vivo long-term kidney monitoring and in vitro urine analysis. The capability of the peptide-based sensor to detect early kidney injury and report on kidney dysfunctional progression is particularly crucial for chemotherapy regimen optimization and timely renoprotective intervention during medication.

https://onlinelibrary.wiley.com/doi/10.1002/anie.202103071