Extended Fused Carbazole-BODIPY, High Brightness NIR Organic Dyes

Area of Science:

• Organic Chemistry
• Materials Science
• Biomedical Imaging

Background:

• Fluorescence bioimaging offers sensitive, non-ionizing visualization but faces limitations with conventional fluorophores due to poor tissue penetration.
• Extending fluorescence to the deeper Near-Infrared II (NIR-II) region (1000-1700 nm) is crucial for overcoming scattering and enhancing tissue penetration.
• Developing bright and stable organic dyes for NIR-II emission remains a significant challenge in bioimaging.

Purpose of the Study:

• To synthesize and characterize a new family of hetero-substituted-fused boron-dipyrromethene (BODIPY) dyes with emission in the NIR-II region.
• To evaluate the photophysical properties, including brightness and stability, of these novel BODIPY derivatives.
• To demonstrate the utility of these dyes for in vivo bioimaging applications, particularly for deep-tissue visualization and tumor detection.

Main Methods:

• Synthesis of fused BODIPY dyes via Stille coupling and silver(I)-mediated oxidative cyclization from a dibromo-diiodo-BODIPY precursor.
• Characterization of photophysical properties: absorption/emission spectra, molar extinction coefficients (ε), and fluorescence quantum yields (Φ).
• Encapsulation of dyes in silica nanoparticles (NPs) and evaluation of their performance in vivo using NIR-II fluorescence imaging in mice.

Main Results:

• Novel fused BODIPY dyes achieved emission maxima up to 852 nm with record brightness and high fluorescence quantum yields (Φ up to 0.73).
• Intense absorption coefficients (ε = 1.8-2.5 × 10⁵ M⁻¹ cm⁻¹) were observed for the synthesized dyes.
• In vivo imaging in mice demonstrated efficient tumor detection at low doses (0.2 nmol) with high tumor-to-muscle ratios (>4) using NPs-encapsulated dyes.

Conclusions:

• The developed hetero-substituted-fused BODIPY dyes represent a significant advancement in NIR-II fluorophores, offering exceptional brightness and stability.
• These dyes, particularly when encapsulated in NPs, enable high-contrast, deep-tissue bioimaging and hold promise for image-guided surgery.
• This work opens new avenues for developing advanced imaging agents for various biomedical applications requiring deep tissue penetration.