Tuning Second Near-Infrared Fluorescence Activation by Regulating the Excited-State Charge Transfer Dynamics Change...

Area of Science:

• Biomedical Imaging
• Fluorescence Spectroscopy
• Chemical Biology

Background:

• Second near-infrared (NIR-II) fluorescence imaging offers high spatial resolution for biopathological studies.
• Developing activatable NIR-II fluorescent probes (AFPs) is challenging due to limited signal activation and complex optimization.
• Existing probes often suffer from insufficient fluorescence "turn-on" ratios in response to biomarkers.

Purpose of the Study:

• To identify a critical determinant for improving the fluorescence "turn-on" ratio of activatable NIR-II fluorescent probes (AFPs).
• To establish a predictive method for streamlining the design and optimization of NIR-II AFPs.
• To demonstrate the clinical potential of optimized AFPs for early disease diagnosis and sensitive metastasis detection.

Main Methods:

• Theoretical identification of excited-state charge transfer dynamics change ratios (δ) as a key factor in AFP responsiveness.
• Design and synthesis of a series of AFPs and their uncaged counterparts (uAFPs).
• Systematic analysis of photophysical characteristics using computational calculations, femtosecond transient absorption spectroscopy, steady-state fluorescence spectra, and fluorescence titration experiments.

Main Results:

• A strong correlation was verified between theoretical/experimental δ values and the fluorescence "turn-on" ratios of activated AFPs.
• The optimal probe (AFP2), guided by δ, demonstrated high sensitivity in early diagnosis of drug-induced liver injury.
• Ultrasensitive detection of small metastatic foci (<2 mm) was achieved in mouse models, outperforming conventional methods.

Conclusions:

• Excited-state charge transfer dynamics change ratios (δ) are a critical determinant for NIR-II AFP responsiveness.
• The δ value can serve as a predictive tool to accelerate the development and optimization of NIR-II AFPs.
• This approach facilitates broader preclinical and translational applications of NIR-II imaging for disease diagnosis and detection.