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 RuII 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 RuII center to yield novel photosensitizers for pH-sensitive 1O2 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 1O2 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.