The aim of the talk is to demonstrate the versatility of the cyclodextrins (CDs) in drastically improving the solubility and cell internalization properties of porphyrins that are used as photosensitizers (PSs) in photodynamic Therapy (PDT).[1] PSs upon illumination and reaction with molecular oxygen found in tissues produce singlet oxygen and other Reactive Oxygen Species (ROS) that are toxic to cells. Conjugation of a lipophilic porphyrin moiety, to a âCD ring[2] affords bimodal systems comprising a red fluorescent-PDT active part (porphyrin) and a molecular carrier part (âCD), that exhibit improved solubility characteristics (several ìM in buffered medium), compared to the insoluble porphyrins, and capacity for cell internalization and imaging as well as for transporting molecules (e. g. tamoxifen, used for estrogen receptor positive cancers). The solubility of the conjugates can be highly elevated (from biologically relevant ìM to a few mM) by exclusive encapsulation of the porphyrin moiety with per-methylâCD, an event characterized by remarkably high binding constants.[3] The resulting tandem system is consequently capable of capturing and carrying a chemotoxic molecule (demonstrated with N-desmethyltamoxifen, a primary metabolite of tamoxifen). The systems show high promise toward a new and advanced modality, Photochemical Internalization (PCI).
[1] Agostinis, P.; Berg, K.; Cengel, K. A.; Foster, T. H.; Girotti, A. W.; Gollnick, S. O.; Hahn, S. M.; Hamblin, M. R.; Juzeniene, A.; Kessel, D.; Korbelik, M.; Moan, J.; Mroz, P.; Nowis, D.; Piette, J.; Wilson, B. C.; Golab, J. CA Cancer J. Clin. 2011, 61, 250-281.
[2] Fraix, A.; Goncalves, A. R.; Cardile, V.; Graziano, A. C. E.; Theodossiou, T. A.; Yannakopoulou, K.; Sortino, S. Chem. Asian J. 2013, 8(11), 2634-2641.
[3] Kano, K.; Nishiyabu, R.; Doi, R. J. Org. Chem. 2005, 70, 3667-3673.
[4] Aggelidou, C.; Theodossiou, T. A.; Yannakopoulou, K. Photochem. Photobiol., 2013, 89, 1011-1019.
Speaker: K. Yannakopoulou
Research Director, Advanced Materials, Physicochemical Processes, Nanotechnology & Microsystems, National Center for Scientific Research "Demokritos"
Time: Wednesday, 19 March 2014, 13:00