Advanced multimodal imaging: FLIM, PLIM, and FluoRaman enabled by novel diarylacetylene probes

Area of Science:

• Chemical Biology
• Molecular Imaging
• Drug Discovery

Background:

• Understanding subcellular localization and physicochemical properties of drug candidates is crucial for optimizing efficacy and mechanism of action.
• Current drug design studies often rely on single imaging modalities, limiting comprehensive analysis.
• There is a need for specialized imaging probes combining luminescence and Raman tags for enhanced signal clarity and multimodal analysis.

Purpose of the Study:

• To showcase the application of advanced imaging modalities for drug design.
• To present novel imaging probes with well-defined photophysical profiles for multimodal imaging.
• To demonstrate the utility of dual-mode imaging tags for drug development.

Main Methods:

• Utilized a suite of advanced imaging modalities: confocal laser scanning microscopy (CLSM), fluorescence lifetime imaging microscopy (FLIM), phosphorescence lifetime imaging microscopy (PLIM), and simultaneous fluorescence and Raman spectroscopy (FluoRaman).
• Employed a series of novel, highly solvatochromic diarylacetylene-based photosensitizers.
• Incorporated alkyne Raman tags into the photosensitizers for dual-mode imaging.

Main Results:

• Demonstrated the capability of multimodal imaging to provide a comprehensive understanding of molecular localization and microenvironment.
• Showcased novel photosensitizers exhibiting diverse subcellular localization.
• Validated the use of combined luminescence and Raman tags for enhanced imaging insights.

Conclusions:

• Multimodal imaging systems offer a more comprehensive understanding of molecular behavior in drug design compared to single modalities.
• The developed diarylacetylene-based photosensitizers with alkyne Raman tags are promising tools for dual-mode subcellular imaging.
• These advanced probes can be used independently or conjugated to drugs for enhanced drug discovery and development.