Photoacoustic (PA) dyes, which absorb near-infrared (NIR) light to generate an ultrasonic signal, can be detected at centimeter depths in tissues with significantly higher resolution than dyes imaged with fluorescence-based methods. As such, PA agents show great promise as research tools for the study of live-animal disease models. However, the development of activatable PA probes has been hampered by the relative scarcity of appropriate PA-active molecular platforms with properties that can be manipulated in a rational manner. Herein we report the chemical tuning of the aza-BODIPY dye platform with respect to their absorbance, fluorescence, and PA properties. We identified a two promising scaffolds: 1) conformationally-restricted aza-BODIPY (CRaB) dyes and 2) sterically relaxed aza-BODIPY dyes that prioritizes three criteria necessary for the design of stimulus-responsive dyes with optimal ratiometric PA response: absorbance at NIR wavelengths, strong PA intensity, and large Δλ upon interaction with the desired stimulus. Using these scaffolds, we synthesized chemically diverse stimulus-responsive PA probes and demonstrated between 2- and 8-fold improvements in theoretical ratiometric response in vitro. This suggests that improvements in PA parameters are generalizable. Finally, we validated the in vitro turnover of each PA probe and demonstrated the in vivo potential of these scaffolds by direct comparison to an established probes for the detection of tumor properties.

Chemical approaches to enhance the photoacoustic properties of stimulus-responsive probes

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.