pH-Activatable Ruthenium(II) Fluorescein Salphen Schiff Base Photosensitizers for Theranostic Applications

Ruthenium(II) polypyridyl complexes exhibit a lack of selectivity toward cancer tissues despite extensive studies as photosensitizers for photodynamic therapy (PDT). Here, we report pH-activatable Ru-II photosensitizers for molecularly targeted PDT by exploiting the higher acidity of tumoral tissue. The fluorescein moiety, well known for its high pH sensitivity, was connected to a Ru-II center to yield novel photosensitizers for pH-sensitive O-1(2) photogeneration. Their ability to photosensitize molecular dioxygen was studied at various pHs and revealed a drastic enhancement from 0.07 to 0.66 of the O-1(2) quantum yield under acidic conditions (pH 7.5 to pH 5.5). Their photocytotoxicity against U2OS osteosarcoma cells was also investigated at pH 5.5 and 7.5 through IC50 determination. A strong enhancement of the photocytotoxicity reaching 930 nM was observed at pH 5.5, which showed the potential of such photosensitizers for pH-activatable PDT.