Design and Characterization of Dual-Modal Fluorinated BODIPY Probes

Multimodal imaging can improve the detection of molecular and pathophysiological changes by combining complementary readouts within a single probe. Here we report the synthesis and characterization of a fluorinated BODIPY dye (F₅₄-BODIPY) designed as dual fluorescence/¹⁹F-MRI imaging agent. The molecular design replaces the native BF₂ unit with multibranched perfluoro-tert-butoxy chains appended at the boron atom via BO hexyloxy linkages, providing 54 magnetically equivalent ¹⁹F nuclei per molecule. Additionally, 2,6-dimethylphenyl groups are introduced at 2,6-positions of F₅₄-BODIPY, and (E)-4-methylstyryl residues at the 3,5-positions extend emission into the far-red region of visible spectrum. This probe was structurally characterized by NMR spectroscopy, and its photophysical properties were evaluated by UV-Vis absorption, fluorescence spectroscopy, and fluorescence quantum yield (Φ_f) measurements. Subsequently F₅₄-BODIPY was encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for dispersion in aqueous media. Co-encapsulation of a second fluorinated phase, namely perfluoro-15-crown-5 ether (PFCE), significantly modified fluorescence properties and introduced a second ¹⁹F-NMR signal, yielding a bimodal nanosystem with dual ¹⁹F-NMR signals and red fluorescence emission for combined fluorescence/¹⁹F-MRI bioimaging.