Blood–Brain Barrier Permeable Photoacoustic Probe for High-Resolution Imaging of Nitric Oxide in the Living Mouse Brain

Abstract

Alternations in the brain nitric oxide (NO) homeostasis are associated with a variety of neurodegeneration diseases; therefore, high-resolution imaging of NO in the brain is essential for understanding pathophysiological processes. However, currently available NO probes are unsuitable for this purpose due to their poor ability to cross the blood–brain barrier (BBB) or to image in deep tissues with spatial resolution. Herein, we developed a photoacoustic (PA) probe with BBB crossing ability to overcome this obstacle. The probe shows a highly selective ratiometric response toward NO, which enables the probe to image NO with micron resolution in the whole brain of living mice. Using three-dimensional PA imaging, we demonstrated that the probe could be used to visualize the detailed NO distribution in varying depth cross-sections (0–8 mm) of the living Parkinson’s disease (PD) mouse brain. We also investigated the therapeutic properties of natural polyphenols in the PD mouse brain using the probe as an imaging agent and suggested the potential of the probe for screening therapeutic agents. This study provides a promising imaging agent for imaging of NO in the mouse brain with high resolution. We anticipate that these findings may open up new possibilities for understanding the biological functions of NO in the brain and the development of new imaging agents for the diagnosis and treatment of brain diseases.

Synthesis and Properties of Bright Red-to-NIR BODIPY Dyes for Targeting Fluorescence Imaging and Near-Infrared Photothermal Conversion

“…Boron dipyrromethene (BODIPY) dyes are widely used as organic fluorophores due to their excellent photochemical stability, adjustable photophysical properties, and versatile structural modifications . BODIPY derivatives have found applications in optoelectronic materials and subcellular-targeting bioimaging and as theranostic reagents. , One effective approach to the red-shift spectrum for BODIPY dyes involves the introduction of aromatic moieties at the periphery of the BODIPY scaffold . For instance, introducing a pyrrolic group at the 3-position of the molecular skeleton has been demonstrated as an effective strategy for meticulously adjusting the photophysical properties and generating novel red to NIR fluorophores .…”

A cyclophane-based host–guest charge transfer complex for NIR-II photothermal conversion

“…Organic near-infrared (NIR) photothermal agents (PTAs), which could convert NIR light into heat energy, have attracted considerable attention due to their great potential applications in photothermal therapy (PTT), 1 photoacoustic imaging, 2 seawater desalination 3 and so on. However, the sophisticated design and laborious synthesis process have greatly limited their development, 4 particularly for that in the NIR-II biowindow (1000–1700 nm), 5 which has deeper tissue penetration for phototheranostics 6 and wider spectrum for solar absorption.…”

Engineering organelle-specific activatable molecules for ultra-fast and reliable in situ mapping of subcellular nitric oxide

“…In order to address the above issues, several recent works based on N -nitrosation strategies which involved BODIPY as a chromophore have caught our attention. 44–47 BODIPY fluorescent dyes have the advantages of good photostability, insensitivity to pH, and high fluorescence quantum yields. 48–52 We expected to construct a generalized platform that could reduce the reaction time of the probe and improve its detection sensitivity, enabling in situ and high-fidelity imaging of NO within various organelles.…”