An N-Alkylpyridinium-Substituted Cyanine Platform for Constructing Renal-Clearable Near-Infrared Fluorogenic Probes.

Area of Science:

• Biomedical Engineering
• Molecular Imaging
• Organic Chemistry

Background:

• Cyanine dyes are crucial for molecular imaging but face toxicity concerns due to slow hepatobiliary clearance.
• Developing renal-clearable probes is essential for safer, long-term disease monitoring.

Purpose of the Study:

• To engineer a novel cyanine imaging platform with efficient renal clearance for real-time disease monitoring.
• To investigate the structure-property relationships of cyanine derivatives for optimized fluorescence and clearance.

Main Methods:

• Molecular engineering of IR780 heptamethine cyanine (CyP) at the meso-position.
• Introduction of pyridinium groups and stimuli-responsive self-immolating linkers.
• Design and synthesis of four representative near-infrared (NIR) fluorescent probes.
• Evaluation of renal clearance, fluorescence response, and application in acute kidney injury (AKI) models.

Main Results:

• Meso-position modification, particularly with pyridinium groups, enhanced renal clearance via electrostatic interactions.
• Methylation of meso-pyridine significantly quenched fluorescence through photoinduced electron transfer (PET) and twisted intramolecular charge transfer (TICT).
• Developed probes exhibited NIR fluorescence "turn-on" response and rapid renal clearance.
• Probes successfully visualized redox imbalance in AKI mouse models with superior sensitivity to SCr and BUN assays.

Conclusions:

• Established a universal, renal-clearable fluorogenic platform based on cyanine dyes.
• Demonstrated the potential for real-time disease monitoring using urine fluorescence readouts.
• Provided insights into cyanine dye structure-property relationships for bioimaging applications.