Renal-Clearable Probe with Water Solubility and Photostability for Biomarker-Activatable Detection of Acute Kidney Injuries via NIR-II Fluorescence and Optoacoustic Imaging

Abstract

Acute kidney injuries (AKI) have serious short-term or long-term complications with high morbidity and mortality rate, thus posing great health threats. Developing high-performance NIR-II probes for noninvasive in situ detection of AKI via NIR-II fluorescent and optoacoustic dual-mode imaging is of great significance. Yet NIR-II chromophores often feature long conjugation and hydrophobicity, which prevent them from being renal clearable, thus limiting their applications in the detection and imaging of kidney diseases. To fully exploit the advantageous features of heptamethine cyanine dye, while overcoming its relatively poor photostability, and to strive to design a NIR-II probe for the detection and imaging of AKI with dual-mode imaging, herein, we have developed the probe PEG3-HC-PB, which is renal clearable, water soluble, and biomarker activatable and has good photostability. As for the probe, its fluorescence (900−1200 nm) is quenched due to the existence of the electron-pulling phenylboronic group (responsive element), and it exhibits weak absorption with a peak at 830 nm. Meanwhile, in the presence of the overexpressed H 2 O 2 in the renal region in the case of AKI, the phenylboronic group is converted to the phenylhydroxy group, which enhances NIR-II fluorescent emission (900−1200 nm) and absorption (600−900 nm) and eventually produces conspicuous optoacoustic signals and NIR-II fluorescent emission for imaging. This probe enables detection of contrast-agent-induced and ischemia/reperfusion-induced AKI in mice using real-time 3D-MSOT and NIR-II fluorescent dual-mode imaging via response to the biomarker H 2 O 2 . Hence, this probe can be used as a practicable tool for detecting AKI; additionally, its design strategy could provide insight into the design of other large-conjugation NIR-II probes with multifarious biological applications.

Precisely Constructing Renal-Clearable and LAP-Activatable Ratiometric Molecular Probes for Early Diagnosis of Acute and Chronic Kidney Injury Via Optimizing Asymmetric DPP Dyes

“…The absorption, emission, and hydrophobic constants of the completely asymmetric dye DPP 11b were between DPP 7a and DPP 7b . This ground-breaking modification had adjusted the lipophilic and hydrophilic properties of the dye DPP 11b , making it have good water solubility, and may also give it appropriate biocompatibility, favorable renal clearance, and renal-targeting ability. − This is extremely important for visualizing kidney imaging. These test results had been verified in density functional theory (DFT) theoretical calculations (Figures S4–S7).…”

“…Fluorescence analysis offers a noninvasive visualization way to monitor and image biomarkers, which helps us understand the pathological process of related diseases and promote their clinical diagnosis and treatment. − Recently, there have been several excellent attempts to diagnose kidney injury using related-biomakers-activated probes. − Investigators optimized some fluorophores with hydrophilic groups such as β-cyclodextrin or PEGn (n = 3–45, poly­(ethylene glycol)) to make the probes sufficiently water-soluble, which is beneficial for increasing its renal clearance and renal-targeting ability. ,, At present, there are few works about renal-clearable and ratiometric fluorescent probes for imaging kidney injury . A ratiometric fluorescent probe with advantages of low interference, high signal-to-noise ratio, and sensitivity is more suitable for monitoring and real-time visualization of active biomarkers of kidney disease. − Moreover, the vast majority of reports just focused on drug-induced AKI.…”

A multifunctional nanoaggregate‐based system for detection of rheumatoid arthritis via Optoacoustic/NIR‐II fluorescent imaging and therapy via inhibiting JAK‐STAT/NF‐κB/NLRP3 pathways

“…To achieve effective visualization of the lesion site and real-time monitoring of the therapeutic effect with high spatial and temporal resolution, a probe that can be activated by in-situ biomarkers in the disease site is highly sought-after. [63][64][65][66][67][68][69] However, imaging probes made from NIR-II chromophores often exhibit aggregation-caused fluorescence quenching, which negatively affects imaging performance, and this is due to their hydrophobic planar structure and the aqueous biological environment. Integrating the aggregation-induced emission (AIE) feature into the probe can overcome this drawback and ensure even more evident fluorescence with enhanced aggregation degree in the aqueous biological milieu.…”

Visualization detection of mycotoxin patulin in fruit juices by a small-molecule fluorescent probe

“…Comparatively, small-molecule-based fluorescent probes are powerful tools that have the advantages of easy operation, rapid response and high sensitivity, and are widely used in food analysis, biological imaging, and environmental monitoring. 50–60 However, to the best of our knowledge, there is no small-molecule fluorescent probe that has been developed for visualizing patulin in food samples.…”