Design of novel sensitizers and investigation of tumor targeting carrier systems for their applications in photodynamic therapy

• Antragsteller: Professor Dr. Bernd Epe
• Fachliche Zuordnung: Pharmakologie
• Förderung: Förderung von 2009 bis 2014
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 119930158

The proposal aims at developing two new classes of photosensitizers, squaraines and croconaines, for application in the photodynamic therapy (PDT) of tumors. Preparatory work has demonstrated that the compounds have long wavelength absorption (>700 nm), good triplet yields, strong phototoxicity and little dark toxicity. The project involves the synthesis of various derivatives and the characterization of their photophysical and photochemical properties (absorption and fluorescence spectra, triplet and singlet oxygen yields, photoproducts). Selected compounds will then be attached to two types of delivery systems for the specific targeting of tumor cells, namely (i) folate-serum albumin conjugates and (ii) nanoparticles (block copolymer micelles) carrying a corona of oligonucleotides, to which folate is bound in the terminal position for receptor-mediated uptake. The loaded delivery systems will be characterized extensively. The cytotoxicity of the photosensitzers in the dark and under irradiation will be studied in various malignant (folate-receptor carrying) tumor cell lines and non-malignant comparisons, both with and without the delivery systems. Cellular uptake will be studied in co-cultures of normal and malignant cells using flow cytometric analysis (FACS). Determinations of (photo)genotoxicity and mechanistic studies will complement the efforts to establish the new drugs as candidates for future in vivo tests.

• DFG-Verfahren: Sachbeihilfen
• Internationaler Bezug: Indien, Niederlande
• Beteiligte Personen: Professor Dr. Andreas Herrmann; Dr. D. Ramaiah