Blood−Brain Barrier Permeable Photoacoustic Probe for HighResolution Imaging of Nitric Oxide in the Living Mouse Brain

血脑屏障可渗透光声探针，用于对活体小鼠大脑中的一氧化氮进行高分辨率成像

主讲人：张俊

Mouse Brain.J. Am. Chem. Soc. 2023, DOI：10.1021/jacs.2c13315Journal of the American Chemical Society ( IF 16.383 )

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 threedimensional 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.

摘要：  

   脑一氧化氮(NO)稳态的改变与多种神经退行性疾病有关；因此，大脑中NO的高分辨率成像对于理解病理生理过程至关重要。然而，目前可用的NO探针不适合用于这一目的，因为它们不能穿过血脑屏障(BBB)或在深部组织中进行空间分辨率成像。在此，我们开发了一种具有血脑屏障穿越能力的光声(PA)探针来克服这一障碍。探针对NO表现出高度选择性的比例响应，这使得探针能够在活体小鼠全脑内以微米级分辨率对 NO 进行成像。通过三维PA成像，我们证明该探针可用于可视化活帕金森病(PD)小鼠大脑不同深度横截面(0 - 8 mm)的NO详细分布。我们还使用探针作为显像剂研究了天然多酚在PD小鼠脑中的治疗特性，并提出了探针筛选治疗剂的潜力。本研究为小鼠脑NO的高分辨率成像提供了一种有前景的显像剂。我们期望这些发现可以为理解NO在脑中的生物学功能和开发新的脑疾病诊断和治疗显像剂开辟新的可能性。