We conducted a comprehensive screening of various pH-sensitive fluorescent dyes to evaluate their potential in forming supramolecular assemblies aimed at reducing toxicity and enhancing water solubility. In addition to physicochemical improvements, we assessed the capability of these newly formed assemblies to selectively target and fluorescently label acidic intracellular organelles, particularly lysosomes and mitochondria.
Furthermore, we investigated the self-assembly behavior of the supramolecular structures, focusing on how the molecular architecture of each dye influences its aggregation properties. Our findings indicate that specific structural features of the fluorescent compounds play a crucial role in the formation of well-defined assemblies.
As part of this study, we also explored the subcellular localization bias of a range of fluorescent dyes. Notably, we identified a series of red-emitting BODIPY derivatives that exhibit minimal organelle-specific bias. These non-biased dyes are particularly suitable for the fluorescent tagging of aminoferrocene-based anticancer prodrugs and active pharmaceutical compounds with molecular weights below 1000 Da.
We further synthesized conjugates of these non-biased BODIPY dyes with aminoferrocenes to examine their intracellular distribution, uptake, and activation profiles. This approach enabled a detailed evaluation of the mechanisms underlying drug activation and localization, thereby contributing valuable insights into the intracellular behavior and therapeutic potential of aminoferrocene-based drug candidates.
We used the selected aminoferrocene-dye conjugates to explore their distribution and transformation in mice. We observed activation of aminoferrocenes and their accumulation in specific tissues. This study provided important information on behavior of aminoferrocenes in vivo.
