![]() ![]() Specifically, it has been hypothesized that Cu 2+ reacts with H 2O 2 via Fenton-like chemistry to yield free radicals which is linked to the assembly of amyloid beta fibrils characteristic of AD. Figure 1Ī potential cause of elevated oxidative stress in the brain of AD mice may be due to Cu dysregulation. The observed ratiometric PA signal change was 1.23 and 0.85 in AD mice and WT mice, respectively. To verify that this was due to probe activation and not dye accumulation, ratiometric analysis was employed. ![]() Relative to age-matched wild-type (WT) animals where the change in the PA signal over time was only 1.02, the corresponding increase was 1.79 in the AD model ( Figure 1c). In their study, PA-HD-H 2O 2 was successfully employed to assess oxidative stress (via H 2O 2 detection) in AD mice ( Figure 1b). An ensuing reaction with H 2O 2 converts the aryl boronate into a phenol, which spontaneously collapses to release PA-HD via quinone-methide elimination chemistry ( Figure 1a). Capping of the resulting dye (named PA-HD) with an aryl boronate trigger led to the development of PA-HD-H 2O 2. (12) Moreover, the authors installed an ortho-chloro group to acidify the phenolic position, which ensures the dye is deprotonated at physiological pH to exhibit a larger extinction coefficient relative to the parent molecule. Toward this end, Chan and co-workers remodeled the canonical hemicyanine dye (HD) by substituting the endocyclic oxygen with a sulfur atom, which red shifts the absorbance of the dye by ∼50 nm and concomitantly decreases the fluorescence quantum yield by 85% (to favor ultrasound (US) production). To detect H 2O 2 in AD brains, it is critical to employ a PA reporter capable of producing a strong signal upon irradiation. ![]() Furthermore, properties such as the kinetics of the probes can be adjusted to accelerate or attenuate reactivity to target transient or longer lasting (or abundant) molecular events, respectively. (4−7) Because ABS exploits the chemical reactivity of the analyte, they can be readily tuned to maximize interaction with the biomarker of interest. In particular, activity-based sensing (ABS) designs have greatly expanded upon what was possible relative to traditional binding-based sensors ( Scheme 1). Since this work over 10 years ago, improvements with respect to instrumentation, dye platforms, and probe designs have been nothing short of revolutionary, lead to major advances in PA cancer imaging. (3) MMP-2-mediated cleavage of the probe at the tumor site separates the components, leading to a change in the PA ratio. Seminal work by Gambhir and co-workers demonstrated the potential of this modality for cancer diagnostics and monitoring by targeting matrix metalloproteinase-2 (MMP-2) activity utilizing a design that consisted of two PA-active molecules appended together by a peptide substrate. ![]()
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