Acceptor engineering for NIR-II dyes with high photochemical and biomedical performance

Area of Science:

• Organic Chemistry
• Materials Science
• Biomedical Imaging

Background:

• Developing stable small-molecule dyes for the second near-infrared window (NIR-II) is crucial for advanced biomedical imaging.
• Existing NIR-II dyes often face challenges with water-solubility and chemical/photostability.
• Donor-acceptor-donor (D-A-D) structures are commonly used but require optimization of building blocks.

Purpose of the Study:

• To design and synthesize a novel electron acceptor (TQT) for enhanced NIR-II dyes.
• To evaluate the stability and optical properties of TQT-based dyes compared to existing materials.
• To demonstrate the in vivo imaging capabilities of the developed NIR-II dye.

Main Methods:

• Synthesis of 6,7-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline (TQT) as an electron acceptor.
• Preparation of sulfonated hydrophilic dye FT-TQT and its complex with fetal bovine serum (FBS).
• Assessment of chemical stability in alkaline conditions and fluorescence quantum yield.
• In vivo imaging of cerebral and tumor vasculature in a mouse model.

Main Results:

• TQT exhibited superior stability in alkaline conditions compared to benzobisthiadiazole (BBT) and PTQ.
• The sulfonated FT-TQT showed a 2.13-fold increase in quantum yield over FT-BBT.
• FT-TQT complexed with FBS displayed a 16-fold enhancement in fluorescence intensity.
• Real-time imaging of cerebral and tumor vessels with micrometer resolution was achieved.
• Dynamic monitoring of tumor vascular disruption post-drug treatment was successfully demonstrated.

Conclusions:

• TQT is an efficient electron acceptor for creating stable and bright NIR-II dyes.
• The acceptor engineering strategy offers a promising route for next-generation NIR-II fluorophores.
• These novel dyes hold significant potential for diverse biomedical applications, including advanced diagnostics and therapeutics monitoring.