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A General Approach to Convert Hemicyanine Dyes into Highly Optimized Photoacoustic Scaffolds for Analyte Sensing **
Author(s) -
Gardner Sarah H.,
Brady Catharine J.,
Keeton Cameron,
Yadav Anuj K.,
Mallojjala Sharath C.,
Lucero Melissa Y.,
Su Shengzhang,
Yu Zhengxin,
Hirschi Jennifer S.,
Mirica Liviu M.,
Chan Jefferson
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202105905
Subject(s) - photoacoustic imaging in biomedicine , analyte , fluorescence , chemistry , plate reader , repurposing , combinatorial chemistry , chromatography , optics , ecology , physics , biology
Most photoacoustic (PA) imaging agents are based on the repurposing of existing fluorescent dye platforms that exhibit non‐optimal properties for PA applications. Herein, we introduce PA‐HD, a new dye scaffold optimized for PA probe development that features a 4.8‐fold increase in sensitivity and a red‐shift of the λ abs from 690 nm to 745 nm to enable ratiometric imaging. Computational modeling was used to elucidate the origin of these enhanced properties. To demonstrate the generalizability of our remodeling efforts, we developed three probes for β‐galactosidase activity (PA‐HD‐Gal), nitroreductase activity (PA‐HD‐NTR), and H 2 O 2 (PA‐HD‐H 2 O 2 ). We generated two cancer models to evaluate PA‐HD‐Gal and PA‐HD‐NTR. We employed a murine model of Alzheimer's disease to test PA‐HD‐H 2 O 2 . There, we observed a PA signal increase at 735 nm of 1.79±0.20‐fold relative to background, indicating the presence of oxidative stress. These results were confirmed via ratiometric calibration, which was not possible using the parent HD platform.