Mitochondria and Neuromast Tagging With Fluorescent Gallium-Triapine Analogues: In Cellulo MP FLIM and Zebrafish Live...

Area of Science:

• Coordination Chemistry
• Bioinorganic Chemistry
• Optical Imaging

Background:

• Thiosemicarbazones are structurally related to clinically relevant compounds with diagnostic potential.
• Fluorescent probes are crucial for visualizing biological processes and metal complex behavior.
• Advanced imaging techniques like multiphoton fluorescence lifetime imaging microscopy (MP-FLIM) offer enhanced resolution and depth penetration.

Purpose of the Study:

• To synthesize novel fluorescent thiosemicarbazone-BODIPY conjugates and their metal complexes (Ga(III), In(III), Fe(III)).
• To investigate the cellular uptake, subcellular localization, and in vivo biodistribution of these complexes using advanced imaging.
• To establish these fluorescent metal complexes as versatile platforms for theranostic applications.

Main Methods:

• Synthesis and characterization of novel tridentate thiosemicarbazone ligands and their metal complexes.
• Solution behavior evaluation under biologically relevant conditions.
• Cellular imaging in HeLa and PC-3 cells using confocal microscopy and MP-FLIM.
• In vivo imaging in zebrafish to determine biodistribution using MP-FLIM.

Main Results:

• Successful synthesis of lipophilic and monocationic metal complexes with 1:2 metal-to-ligand stoichiometry.
• Demonstrated preferential mitochondrial localization for specific gallium complexes in cancer cells.
• Revealed selective labeling of neuromast structures in zebrafish, indicating specific biodistribution.
• Provided in vitro and in vivo insights into the speciation, stability, and spatial distribution of the complexes.

Conclusions:

• Novel fluorescent thiosemicarbazones serve as versatile platforms for studying metal complex behavior.
• Advanced optical imaging techniques, particularly MP-FLIM, are effective for visualizing metal complex biodistribution.
• These findings open new avenues for developing advanced theranostic agents.