<p>In the context of
deep-tissue disease biomarker detection and analyte sensing of biologically
relevant species, the impact of photoacoustic imaging has been profound. However,
most photoacoustic imaging agents to date are based on the repurposing of
existing fluorescent dye platforms that exhibit non-optimal properties for photoacoustic applications (e.g., high
fluorescence quantum yield). Herein, we introduce two effective modifications to
the hemicyanine dye to afford PA-HD, a new dye scaffold optimized for photoacoustic
probe development. We observed a significant increase in the photoacoustic
output, representing an increase in sensitivity of 4.8-fold and a red-shift of
the λ<sub>abs</sub> from 690 nm to 745 nm to enable ratiometric
imaging. Moreover, to demonstrate the generalizability and utility of our
remodeling efforts, we developed three probes using common analyte-responsive
triggers for beta-galactosidase activity (PA-HD-Gal), nitroreductase activity (PA-HD-NTR),
and hydrogen peroxide (PA-HD-H<sub>2</sub>O<sub>2</sub>). The performance of
each probe (responsiveness, selectivity) was evaluated <i>in vitro</i> and <i>in
cellulo</i>. To showcase the enhance properties afforded by PA-HD for <i>in
vivo</i> photoacoustic imaging, we employed an Alzheimer’s disease model to detect
H<sub>2</sub>O<sub>2</sub>. In particular, the photoacoustic signal at 735 nm in
the brains of 5xFAD mice (a murine model of Alzheimer’s disease) increased by
1.72 ± 0.20-fold relative to background indicating the
presence of oxidative stress, whereas the change in wildtype mice was
negligible (1.02 ± 0.14). These results were
confirmed via ratiometric calibration which was not possible using the parent
HD platform.</p>
Modulation of glucose uptake and insulin sensitivity in insulin resistant in vitro Alzheimer’s Disease model by vitamin D and E
