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

Angew Chem Int Ed Engl. 2021 Aug 16;60(34):18860-18866. doi: 10.1002/anie.202105905. Epub 2021 Jul 1.

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 that features a 4.8-fold increase in sensitivity and a red-shift of the λabs 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 H2 O2 (PA-HD-H2 O2 ). 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-H2 O2 . 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.

Keywords: Alzheimer's disease; acoustogenic probe; analyte sensing; hydrogen peroxide; photoacoustic imaging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / metabolism
  • Animals
  • Brain / diagnostic imaging
  • Carbocyanines / chemistry*
  • Disease Models, Animal
  • Fluorescent Dyes / chemistry*
  • Hydrogen Peroxide / chemistry
  • Mice
  • Molecular Structure
  • Optical Imaging*
  • Oxidative Stress
  • Photoacoustic Techniques*

Substances

  • Carbocyanines
  • Fluorescent Dyes
  • tetramethylene hemicyanine
  • Hydrogen Peroxide