6EET Moleküler Algılayıcısının Modüler Tasarımı Coşkun, A.; Akkaya, E. U. J. Am. Chem. Soc. 2005, 127,
7Modulation of EET via cation binding Bilkent UniversityModulation of EET via cation bindingCoskun, A.; Akkaya, E. U. J. Am. Chem. Soc., 2006, 128,
8Donör gruptan enerji aktarımının modülasyonu HgGuliyev, R.; Coskun, A.; Akkaya, E. U. J. Am. Chem. Soc., 2009, 131, 000.
9Nanotechnology Takes Aim at Cancer Bilkent UniversityNanotechnology Takes Aim at Cancer
10Dendrimers as versatile platforms Bilkent UniversityDendrimers as versatile platforms
11A very brief history of photodynamic therapy Bilkent UniversityA very brief history of photodynamic therapyOscar Raab/von Tappeiner (1900)A particular dye (acridine)+ Light, kills aquatic organisms.Jodlbauer/von Tappeiner (1904)“photodynamische wirkung” oxygen is also required for activityMeyer-Betz (1912)Demonstration of photodynamic activity in human. 200 mg hematoporphyrin(redness and oedema)Porphyria connectionHigh concentration levels of protoporphyrin in plasma.FDA approval (1995)Photophyrin was approved for esophogal cancer.
12Meyer-Betz: experiment on self Bilkent UniversityMeyer-Betz: experiment on self
13Practice of Photodyamic Therapy Bilkent UniversityPractice of Photodyamic TherapyIn December 1995, the FDA approved a photosensitizing agent called porfimer sodium (Photofrin) combined with light from a laser for treating patients with cancer of the esophagus in the following situations:To relieve symptoms of esophageal cancer, including difficulty swallowing, that are caused by a tumor obstructing (blocking) the esophagusTo treat esophageal cancer that cannot be treated with laser therapy aloneIn 1998, the FDA approved porfimer sodium for two additional uses:To treat endobronchial (affecting the lining of the bronchi) non-small cell lung cancer that is microinvasive (has minimal spread of cancer cells) for patients who cannot have other types of treatment such as surgery or radiation therapyTo reduce obstruction and to palliate (ease) symptoms in people with endobronchial non-small cell lung cancer that is either completely or partially obstructing the bronchi
14From “Scientific American, January 2003* Bilkent UniversityFrom “Scientific American, January 2003** New Light on Medicine
20Applications of PDT Potential Cancer Therapy – Endobronchial cancer Bilkent UniversityApplications of PDTPotential Cancer Therapy– Endobronchial cancer– Esophageal cancer– Skin Cancers– Breast Cancers– Colorectal Tumors– Gynecologic malignanciesOther Diseases– Cardiovascular (e.g., alternative to angioplasty)– Chronic skin diseases [e.g. Psoriasis (in development)]– Autoimmune (e.g. Rheumatoid arthritis)– Macular degeneration– Antibacterial (wound healing, oral cavity)– Vaccine – especially anticancer vaccines– Endometriosis– Precancerous conditions
21The light activated drugs in the market or in development Bilkent UniversityThe light activated drugs in the market or in development
22Ideal photosensitizer for PDT Bilkent UniversityIdeal photosensitizer for PDTis a chemical compound that can be excited by light of a specificwavelengthA good photosensitizer should have:Little or no toxicity in the darkGood pharmokinetic behaviour (high selectivity for tumour tissue andeasy elimination from the body)A constant composition (preferably a single achiral substance)A high triplet quantum yield and a triplet energy with efficient energytransfer to produce singlet oxygenAnd red absorption to take advantage to deep light penetration
23Dyes with known sensitizer activity Bilkent UniversityDyes with known sensitizer activityQuinone derivatives : Hypericin (590 nm), Acriflavin (460 nm).Acridine dyes: Acridine Orange (492 nm)Phenothiazine: Methylene blue (660 nm)Xanthene dyes: Rose Bengal (549 nm)Cyanine dyes: merocyanine (540 nm)-Porphyrins, Chlorins and Bacteriochlorin: Hematoporphyrin (645 nm)-Phthalocyanines: Phthalocyanine (698 nm),tetra-t-butylnaphthocyanine (784 nm)
24Red light activation of the sensitizer Bilkent UniversityRed light activation of the sensitizerFiltered red light l> 600 nm (2005)Red LED array l= 625 nm (2006)
25Boradiazaindacene based PDT reagents Bilkent UniversityBoradiazaindacene based PDT reagents
26TARGET PHOTOSENSITIZER Enhanced solubility in aqueous mediaThe presence of heavy atoms providesenhanced intersystem crossingLong wavelength absorption ( nm)
27Degradation of the singlet oxygen trap Bilkent UniversityDegradation of the singlet oxygen trapwith 9 nM sensitizer
28Standard MTT assay of photoinduced Bilkent UniversityStandard MTT assay of photoinducedcytotoxicityPercent viability as determined by a standard MTT assay. “Control” corresponds to assay data obtained with K562 cells kept in full medium in dark at 37 oC in an incubator. The other black bars show cell viability at different sensitizer concentrations in dark. Red bars show percent viability at the indicated concentrations under 4 hr irradiation with red LED at 2.5 mW/cm2 fluence rate, followed by 20 hr incubation in dark at 37oC. Percent viability values shown here are the averages of 4 runs.