A Photoacoustic Probe with Blood‐Brain Barrier Crossing Ability for Imaging Oxidative Stress Dynamics in the Mouse Brain

Abstract

Spatiotemporal assessment of the oxidative stress dynamics in the brain is crucial for understanding the molecular mechanism underlying neurodegenerative diseases. However, existing oxidative stress probes have poor blood‐brain barrier permeability or poor penetration depth, making them unsuitable for brain imaging. Herein, we developed a photoacoustic probe that enables real‐time imaging of oxidative stress dynamics in the mouse brain. The probe not only responds to oxidative stress in a reversible and ratiometric manner, but it can also cross the blood‐brain barrier of the mouse brain. Notably, the probe displayed excellent photoacoustic imaging of oxidative stress dynamics in the brains of Parkinson's disease mouse models. In addition, we investigated the antioxidant properties of natural polyphenols in the brain of a Parkinson's disease mouse model using the probe as an imaging agent and suggested the potential of the probe for screening anti‐oxidative stress agents.

Reversible Dual Fluorescence-Lifetime Imaging of Mitochondrial GSH and Microviscosity: Real-Time Evaluation of Ferroptosis Status

“…The most classic reversible fluorescent for GSH is based on the Michael addition of GSH to α,β-unsaturated ketones or amides . Notably, most of them are designed on the coumarin scaffold. , BODIPY dyes are a family of promising fluorophores that show excellent photophysical performances and rich synthetic protocols. − We proposed to introduce α,β-unsaturated ketone/amide into the BODIPY cores to expand and optimize the design of dynamic fluorescent probes. Therefore, compounds 1 – 8 were synthesized.…”

A Reversible Fluorescent Probe for In Situ Monitoring Redox Imbalance during Mitophagy

“…Compared to traditional methods, fluorescent probes have become powerful tools for detection and bioimaging of ROS with simple operation, high sensitivity and selectivity, and good biocompatibility. − To this end, various H 2 O 2 fluorescent probes have been exploited based on boric acid/ester deprotection, sulfonyl oxidation, Baeyer–Villiger-type reaction, and Mislow–Evans rearrangement. − In addition, mitochondria-specific H 2 O 2 probes were successfully exploited for bioimaging. − However, all of these probes are based on irreversible reactions, which are suitable for one-shot measurement but cannot provide information on mitochondrial H 2 O 2 dynamics. , Although a few reversible H 2 O 2 fluorescent probes have been reported, they showed comparatively low sensitivity and slow reaction kinetics (Table S1). − Therefore, it is urgent to develop highly sensitive and fast-responding fluorescent probes for reversible monitoring of mitochondrial H 2 O 2 dynamics.…”

“…26−31 However, all of these probes are based on irreversible reactions, which are suitable for one-shot measure-ment but cannot provide information on mitochondrial H 2 O 2 dynamics. 32,33 Although a few reversible H 2 O 2 fluorescent probes have been reported, they showed comparatively low sensitivity and slow reaction kinetics (Table S1). 34−37 Therefore, it is urgent to develop highly sensitive and fastresponding fluorescent probes for reversible monitoring of mitochondrial H 2 O 2 dynamics.…”

Single Atom Stabilization of Phosphinate Ester‐Containing Rhodamines Yields Cell Permeable Probes for Turn‐On Photoacoustic Imaging**

“…The BODIPY, [10,11,12,13,14] hemicyanine, [3,15,16,17] and cyanine scaffolds [18] have been the primary small-molecule dyes employed for PAI due to compatibility of their maximal absorbance with commercial PAI instrumentation. Recent chemistry-focused efforts have leveraged activity-based sensing approaches [19,20,21,22,23] to develop turn-on or acoustogenic small molecule PA reporters from these scaffolds.…”