Synthesis of BODIPYs using organoindium reagents and survey of their cytotoxicity and cell uptake on nervous system cells

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• First examples of functionalization of BODIPYs at beta positions by cross-coupling reactions using organoindium reagents. • The viability of BODIPYs bearing benzonitrile and thien-2-yl moieties towards SH-SY5Y cells remain above 80 % (0–50 μM). • BODIPY 11 was encapsulated in liposomes exhibiting particle-size of120 nm (PDI 0.05), ζ of 54.69 mVand excellent stability. • Fluorescence imaging on U87 cells showed that BODIPY 11 appeared to be localized in the cytoplasm due to its brightness. In this study, a series of BODIPY dyes were synthesized, containing various substituents at meso position. Further functionalization of the BODIPY framework at C2 and C2–C6 position(s) by palladium-catalysed cross-coupling reactions using organoindium reagents (R 3 In) was efficiently assessed, starting from C2(6)-halogenated BODIPYs, and their optical properties were measured. The cytotoxicity of BODIPY dyes on SH-SY5Y neuronal cells by MTT assay showed that those compounds bearing thien-2-yl and benzonitrile moieties at meso position, exhibited great efficiency in maintaining cell viability under all tested conditions (up to 50 µM for 24 h and 48 h). Furthermore, nanoliposomal encapsulation of a hydrophobic BODIPY, incorporating bis(trifluoromethyl)phenyl substituents at C2 and C6 positions, through the lipid-extrusion method was addressed. The liposomes exhibited spherical shape as observed in cryo-TEM image, with average particle size of 120 nm (average PdI 0.05) and Zeta potential 54.69 mV by DLS measurements. Simple incubation of gliobastoma U-87 cells with prepared liposomes led to efficient internalization, and visualization of brightness BODIPY in cytoplasm using fluorescence confocal microscopy, demonstrating encapsulation enhance biocompatibility of the hydrophobic BODIPY as preliminary approximation for further biomedical applications.