Light in the second near-infrared window, especially beyond 1500 nm, shows enhanced tissue transparency for high-resolution in vivo optical bioimaging due to decreased tissue scattering, absorption, and autofluorescence. Despite some inorganic luminescent nanoparticles have been developed to improve the bioimaging around 1500 nm, it is still a great challenge to synthesize organic molecules with the absorption and emission toward this region. Here, we present J-aggregates with 1360 nm absorption and 1370 nm emission formed by self-assembly of amphiphilic cyanine dye FD-1080 and 1,2-dimyristoyl-sn-glycero-3-phosphocholine. Molecular dynamics simulations were further employed to illustrate the self-assembly process. Superior spatial resolution and high signal-to-background ratio of J-aggregates were demonstrated for noninvasive brain and hindlimb vasculature bioimaging beyond 1500 nm. The efficacy evaluation of the clinically used hypotensor is successfully achieved by high-resolution in vivo dynamic vascular imaging with J-aggregates.

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.

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 (ɛ max Φ f > 1000 nm < 10 M À 1 cm À 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 (ɛ max Φ f > 1000 nm � 60 M À 1 cm À 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 noninvasively 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.

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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.