We developed „theranostic”“ components ( therapy and diagnostic in parallel) with high specificity and selectivity of imaging (with e.g. Cy7) and a therapeutic intervention with temozolomide [TMZ], in the target tissue without damage of the surrounding cells as reviewed in: Wiessler et al. The Diels-Alder-Reaction with Inverse-Electron-Demand- a Review- of an efficient & attractive Click-Reaction Concept. IJPSR, 2013; Vol. 4(10): 3678-3698.
The development of such prospective image processing systems in molecular diagnostics and of pharmacologically active ingredients for patient-specific theranostic approaches requires not only high demands on quality, safety, and specificity but also, rapid, efficient and irreversible ligation routes during the synthesis of future pharmaceuticals. The Diels-Alder ligation reaction with inverse electron demand (DARinv) is a technology not restricted to medical applications, but valuable in selective modification of polymers by functionalization of,organic and inorganic surfaces and micro arrays. The DAR principle and its chemical potential for the pharmaceutical research were investigated. Dependent on the chemical properties of the dienes and the dienophiles the reaction led to different, but preferred variants. In future, dienes, functionalized with pharmacologically active molecules are definitely conceivable. The functionalization of a diaryl-tetrazine with “old fashiond” drugs like TMZ and the effects of the DARinv.reaction product were first documented as an exemplarily reformulation of established drugs. (Waldeck et al. TMZ-BioShuttle – a reformulated Temozolomide, Int. J. Medic Sci 2008, 5 (5):273-284)
These chemical reaction products are able to overcome cellular membrane barriers on the way to a save and efficient transfer of therapeutic and / or diagnostic cargos into target cells and tissues. It is important to point out that this DARinv technology is not restricted to application and easier handling of our developed BioShuttle delivery platform. Wiessler et.al Theranostic cRGD-BioShuttle Constructs Containing Temozolomide- and Cy7 For NIR-Imaging and Therapy. Theranostics 1:381-394, 2011.