A General Approach to Convert Hemicyanine Dyes into Highly Optimized Photoacoustic Scaffolds for Analyte Sensing.

Abstract

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 which features an increase in sensitivity of 4.8-fold and a red-shift of the λ abs from 690 nm to 745 nm to enable ratiometric imaging. Computational modelling was employed to elucidate the origin of these enhanced properties. Moreover, 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. Additionally, we employed a murine model of Alzheimer s disease to test PA-HD-H 2 O 2 . In this latter example, 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.