Mitochondria Targeting Selenophene Modified BODIPY-Based Photosensitizers for Treatment of Hypoxic Cancer Cells.

Two red absorbing, water soluble and mitochondria (MT) targeting selenophene substituted BODIPY based photosensitizers (PSs) were realized (BOD-Se, BOD-Se-I) and their potential as photodynamic therapy (PDT) agents were evaluated. BOD-Se-I showed higher 1O2 generation yield thanks to the enhanced heavy atom effect and this derivative was further tested detailly in cell culture studies under both normoxic and hypoxic conditions. BOD-Se-I not only effectively functioned under hypoxic conditions but also showed highly selective photocytotoxicity towards cancer cells. The selectivity is believed to arise from difference in mitochondrial membrane potentials of healthy and cancerous cells. To best of our knowledge this marks the first example of a MT targeted BODIPY PS that functions under hypoxic conditions. Remarkably, thanks to the design strategy all these properties where realized by a compound that was synthesized in only five steps with 32% overall yield. Hence, this material holds great promise towards realization of next generation PDT drugs towards treatment of hypoxic solid tumors.