Early detection of kidney disease is of vital importance due to its current prevalence worldwide. Fluorescence imaging, especially in the second near-infrared window (NIR-II) has been regarded as a promising technique for the early diagnosis of kidney disease due to the superior resolution and sensitivity. However, the reported NIR-II organic renal-clearable probes are hampered by their low brightness (ϵ_maxΦ_f>1000 nm<10 M⁻¹cm⁻¹) and limited blood circulation time (t_1/2<2 h), which impede the targeted imaging performance. Herein, we develop the aza-boron-dipyrromethene (aza-BODIPY) brush macromolecular probes (Fudan BDIPY Probes (FBP 912)) with high brightness (ϵ_maxΦ_f>1000 nm≈60 M⁻¹ cm⁻¹), which is about 10-fold higher than that of previously reported NIR-II renal-clearable organic probes. FBP 912 exhibits an average diameter of ≈4 nm and high renal clearance efficiency (≈65 % excretion through the kidney within 12 h), showing superior performance for non-invasively diagnosis of renal ischemia-reperfusion injury (RIR) earlier than clinical serum-based protocols. Additionally, the high molecular weight polymer brush enables FBP 912 with prolonged circulation time (t_1/2≈6.1 h) and higher brightness than traditional PEGylated renal-clearable control fluorophores (t_1/2<2 h), facilitating for 4T1 tumor passive targeted imaging and renal cell carcinoma active targeted imaging with higher signal-to-noise ratio and extended retention time.

https://onlinelibrary.wiley.com/doi/10.1002/anie.202114273