pH-Activatable Singlet Oxygen-Generating Boron-dipyrromethenes (BODIPYs) for Photodynamic Therapy and Bioimaging

Singlet oxygen can severely damage
biological tissue, which is
exploited in photodynamic therapy (PDT). In PDT, the effective range
is limited by the distribution of the photosensitizer (PS) and the
illuminated area. However, no distinction is made between healthy
and pathological tissue, which can cause undesired damage. This encouraged
us to exploit the more acidic pH of cancerous tissue and design pH-controllable
singlet oxygen-generating boron-dipyrromethene (BODIPY) dyes. A pH
sensitivity of the dyes is achieved by the introduction of an electronically
decoupled, photoinduced electron transfer (PET)-capable subunit in
meso-position of the BODIPY core. To favor triplet-state formation
as required for singlet oxygen generation, iodine substituents were
introduced at the chromophore core. The resulting pH-controlled singlet
oxygen-generating dyes with pKa values
in the physiological range were subsequently assessed regarding their
potential as pH-controlled PS for PDT. Using HeLa cells, we could
successfully demonstrate markedly different pH-dependent cytotoxicities
upon illumination.