A Conformationally Restricted Aza-BODIPY Platform for Stimulus-Responsive Probes with Enhanced Photoacoustic Properties
Year: 2019
Type: article
Abstract: 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 synthesized and evaluated six modifications to the aza-BODIPY dye platform with respect to their absorbance, fluorescence, and PA properties. We identified a promising c onformationally r estricted a za- B ODIPY (CRaB) scaffold 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 this scaffold, we synthesized three 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 CRaB PA probe and demonstrated the in vivo potential of the CRaB scaffold by direct comparison to an established hypoxia-responsive probe for the detection of tumor hypoxia.
DOI: 10.1021/jacs.9b06694
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Funders: National Science Foundation, National Natural Science Foundation of China, University of Illinois at Urbana-Champaign, National Institute of General Medical Sciences, National Institute of Biomedical Imaging and Bioengineering, Division of Chemistry, Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana-Champaign
OpenAlex ID: W2982292832