BORDPRN (BODIPY) BLEKLER KMYASI VE UYGULAMALARIEngin Umut Akkaya Bilkent niversitesi, Kimya Blm &UMAM-Malzeme Bilimi ve Nanoteknoloji Enstits06800 Ankara E-mail: eua@fen.bilkent.edu.tr

Bodipy: A versatile chromophore

Derivatization of the BODIPY coreAkkaya(2009)

Our First Encounter with Bodipy

Reverse PET/Bipyridyl-Bodipy

EET Molekler Alglaycsnn Modler Tasarm Cokun, A.; Akkaya, E. U. J. Am. Chem. Soc. 2005, 127, 10464.

Coskun, A.; Akkaya, E. U. J. Am. Chem. Soc., 2006, 128, 14474-14475 Modulation of EET via cation binding

Donr gruptan enerji aktarmnn modlasyonuGuliyev, R.; Coskun, A.; Akkaya, E. U. J. Am. Chem. Soc., 2009, 131, 000.

Nanotechnology Takes Aim at Cancer

Dendrimers as versatile platforms

Oscar 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 connection High concentration levels of protoporphyrin in plasma.FDA approval (1995)Photophyrin was approved for esophogal cancer.A very brief history of photodynamic therapy

Meyer-Betz: experiment on self

Practice of Photodyamic Therapy

From Scientific American, January 2003** New Light on Medicine

The Jablonski diagramhttp://www.monos.leidenuniv.nl/smo/index.html?basics/photophysics.htm

Light penetration in mammalian tissues

Enhanced permeation and retention- EPR

http://www.uphs.upenn.edu/radiology/depa/MICL/MolecularImagingChemistry2.htmIn vivo veritas !

PDT: How the tumor dies

Potential 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 conditionsApplications of PDT

The light activated drugs in the market or in development

is a chemical compound that can be excited by light of a specific wavelengthA good photosensitizer should have:

Little or no toxicity in the dark

Good 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 energy transfer to produce singlet oxygen

And red absorption to take advantage to deep light penetration

Ideal photosensitizer for PDT

Quinone 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)

Dyes with known sensitizer activity

Red light activation of the sensitizerFiltered red light l> 600 nm (2005)Red LED array l= 625 nm (2006)

Boradiazaindacene based PDT reagents

TARGET PHOTOSENSITIZEREnhanced solubility in aqueous media The presence of heavy atoms provides enhanced intersystem crossingLong wavelength absorption (650-680 nm)

Degradation of the singlet oxygen trap with 9 nM sensitizer

Percent 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.Standard MTT assay of photoinduced cytotoxicity

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