Maximizing the thiol-activated photodynamic and fluorescence imaging functionalities of theranostic reagents by modularization of Bodipy-based dyad triplet photosensitizers.

To maximize both the activatable singlet oxygen (1O2) production and fluorescence of theranostic photodynamic (PDT) reagents, herein we propose a modularized molecular structural profile, i.e. the intersystem crossing (ISC) and fluorescence functionalities were accomplished with different modules in a dyad, thus enabling the activated 1O2 production yield (ΦΔ, PDT) and the fluorescence yield (ΦF) to both approach 100%. The PDT and the fluorescence were caged with a thiol-cleavable disulfide bond (-S-S-) linker and an electron trap (2,4-dinitrobenzenesulfide, DNBS). This new molecular structural profile is different from that of conventional theranostic PDT reagents, which are based on a single chromophore for both PDT and fluorescence; thus, the limitation of ΦΔ + ΦF = 100% exists for only half of our new molecular profile. To this end, six Bodipy dyads were prepared. The photophysical properties of the dyads were studied with steady state absorption, fluorescence and nanosecond transient absorption spectroscopy. The dyads show weak PDT and luminescence, due to the caging effect. In the presence of thiols (GSH or Cys), cleavage of the disulfide linker and DNBS occurs, and the PDT and fluorescence modules are activated simultaneously (ΦF: 1.3% → 47.6%; ΦΔ: 16.7% → 71.5%). These results are useful in designing activatable PDT/fluorescence imaging theranostic reagents.