Mitochondria-Targeting Selenophene-Modified BODIPY-Based Photosensitizers for the Treatment of Hypoxic Cancer Cells |
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Authors: | Osman Karaman Toghrul Almammadov M. Emre Gedik Dr. Gurcan Gunaydin Dr. Safacan Kolemen Dr. Gorkem Gunbas |
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Affiliation: | 1. Department of Chemistry, Middle East Technical University (METU), 06800 Ankara, Turkey;2. Department of Chemistry, Koc University, 34450 Istanbul, Turkey;3. Department of Basic Oncology, Hacettepe University, 06100 Ankara, Turkey |
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Abstract: | 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 in detail 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 differences in mitochondrial membrane potentials of healthy and cancerous cells. To the 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 for the realization of next-generation PDT drugs for the treatment of hypoxic solid tumors. |
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Keywords: | photodynamic therapy BODIPY singlet oxygen hypoxia mitochondria |
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