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

KARAMAN O., Almammadov T., Gedik M. E., GÜNAYDIN G., Kolemen S., Gunbas G.

CHEMMEDCHEM, vol.14, no.22, pp.1879-1886, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 14 Issue: 22
  • Publication Date: 2019
  • Doi Number: 10.1002/cmdc.201900380
  • Journal Name: CHEMMEDCHEM
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1879-1886
  • Keywords: photodynamic therapy, BODIPY, singlet oxygen, hypoxia, mitochondria, PHOTODYNAMIC THERAPY, DERIVATIVES, EFFICIENT, OXYGEN
  • Hacettepe University Affiliated: Yes


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 O-1(2) 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.