Designing Excited States for Photodynamic Therapy of Cancer
and Live Cell Imaging
Safacan Kölemen, PhD
University of California, Berkeley
Department of Chemistry
Photodynamic therapy (PDT) is a developing treatment modality for certain malignant, premalignant and nonmalignant indications. In PDT, therapeutic action is achieved by the generation of cytotoxic singlet oxygen (SO) upon the irradiation of well-designed photosensitizers. In order to get effective inter-system crossing, which is highly needed for singlet oxygen generation, common strategy is to incorporate heavy atoms on sensitizers. However, presence of heavy atoms increases the dark toxicity, which is not desired in practical applications. Here, we are introducing a new concept for activatable heavy atom free sensitization of PDT by designing novel orthogonal BODIPY-based photosensitizers. Although PDT of cancer has been considered as a promising therapeutic approach for decades, broader acceptance by the medical community and applicability is hampered due to two major reasons; (i) poor penetration depth of the irradiation light and (ii) hypoxic nature of cancer cells. Herein we are also addressing these two everlasting problems of PDT by the use of gold nanoparticles.
Fluorescence imaging of live cells by using small molecular probes offers great advantages such as spatial and temporal resolution, high selectivity/sensitivity and simple operations. In the second part of this talk, development of fluorescent molecular probes for synaptic transmission (neurotransmission) monitoring and copper detection in live cells will be introduced. Synaptic transmission is an essential process for neuronal communication in the nervous system and it takes place at synapses with the help of synaptic vesicles. During the neurotransmission, interior pH of the synaptic vesicles changes. We are using this pH change to visualize synaptic transmission by employing pH-sensitive fluorescent molecular probes. On the other hand, copper, as a result of its redox activity plays significant roles in important biological processes such as energy generation, oxygen transport, cellular metabolism and signal transduction, which makes it vital for the life of eukaryotic organisms. However, when the redox activity of copper is misregulated, it can also lead to aberrant generation of reactive oxygen species (ROS) that has been linked to aging and different disease states including genetic disorders like Menkes and Wilson’s diseases, neurodegenerative diseases like Alzheimer’s, and Parkinson’s diseases, and metabolic disorders such as diabetes and obesity. Thus development of copper-selective molecular probes with their unique fluorescence output provides a potentially powerful toolbox that allows for the mapping of labile metal pools and the study of the roles of these dynamic fluxes in different applications.
Dr. Safacan Kölemen graduated from Chemistry Department at Bilkent University in 2008. He completed his MSc studies at the same department in 2010. He received his PhD in 2014 from Material Science and Nanotechnology department (UNAM) at Bilkent University, where he worked under the supervision of Prof. Engin Umut Akkaya on designing photosensitizers for photodynamic therapy of cancer. Then he joined to Chris Chang’s lab at University of California, Berkeley as a postdoctoral researcher. His current research focuses on development of fluorescent probes for various applications in biological systems.