Development of chemical tools for studying biology with light: Photoactivatable donors and photoacoustic probes

Chemical tools are essential for the study of complex biological processes. Generally, this is achieved through the controlled perturbation of a biological system and the observation of an effect. In this work, we present the development of molecular tools for both of these aspects. The first chapter highlights our rational development of a photo-controlled formaldehyde do-nor with an internal fluorescence response upon activation. This tool enabled us to establish an assay for the quantification of the released reactive carbon species into the intracellular space. Using this unique approach, we evaluated the dose-dependent impairment of HEK293 cells by formaldehyde in a wound healing assay and showed the potential cytotoxicity of common formaldehyde-releasing prodrug approaches. The second and third chapter summarize our ap-proaches towards activatable contrast agents for photoacoustic imaging, an emerging deep-tissue imaging modality. To address a lack of modular activatable probes for this imaging technique, we combined the analyte specificity of DNA aptamers with commercially available fluorophores to show the feasibility of a general approach. For our proof-of-concept study, we used a thrombin-selective aptamer and were able to show a selective modulation of the photo-acoustic signal upon exposure to thrombin in vitro and in vivo. In addition, we are currently developing new dye platforms, imaging techniques and probes for photoacoustic imaging.LimitedAuthor requested closed access (OA after 2yrs) in Vireo ETD syste