Exploring new mitochondria-targetable theragnostic styrylBODIPYs

BODIPYs involving styryl groups at the 3/5 BODIPY positions have demonstrated interest as readily accessible red-to-NIR chromophoric platforms for the development of smarter dyes for advancing biophotonic applications, including smarter photosensitizers for photodynamic therapy (PDT) and phototheragnosis.

In this context, we have recently discovered the capability of highly-fluorescent 3-styryl- and 3,5-distyrylBODIPYs, bearing tripheynylphosphonium groups at their styryl moieties, to serve as a new type of heavy-atom-free red phototheragnostic agents, due to enhanced PDT triggered by their selective accumulation into mitochondria. The specific targeting of these organelle is achieved by the role of the tripheynylphosphonium groups, due to the well-known mitochondria membrane potential (160–180 mV; negative inside).

We were interested in exploring whether this amazing PDT activity, surprisingly coming from a highly fluorescent dye, could be also achieved by using other delocalized cations instead of tripheynylphosphonium or, even, non-delocalized cations (e.g., quaternary ammonium salts). To this aim, we found it interesting to carry out a preliminary study on the use of styryl moieties functionalized with ammonium cations (directly linked to the styryls or through suitable spacers avoiding electronic conjugation) for the rapid construction of new mitochondria-targetable phototheragnostic red styrylBODIPYs. This communication reports the preliminary results obtained from such a study, which could allow designing improved red-to-NIR PDT agents free of heavy atoms.

We define a new strategy to develop, through a straightforward and low cost synthetic protocol, two BODIPYs with red-absorption and good fluorescence ability. These novel BODIPYs, were functionalized by Knoevenagel condensations with styryl moieties that present non-delocalized cations (trimethylammonium salt) attached to the BODIPY through a spacer, or directly linked. This approach has been exemplified by the development of new dyes for cell bioimaging. The preliminary results over one them show, successfully internalize into Hela cells and accumulate in the mitochondria. In vitro suitability for photodynamic therapy (PDT) was also analyzed in this derivative and confirmed that it’s a mitochondria-targetable phototheragnostic red styrylBODIPYs.