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荧光和光声(FL/PA)双模探针:响应活性氧(ROS)用于动脉粥样硬化斑块成像。

Fluorescence and photoacoustic (FL/PA) dual-modal probe: Responsive to reactive oxygen species (ROS) for atherosclerotic plaque imaging.

机构信息

Shanghai Key Laboratory of Functional Materials Chemistry, Key Laboratory for Advanced Materials and Institute of Fine Chemicals, Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 200237, China.

Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200030, China.

出版信息

Biomaterials. 2025 Feb;313:122765. doi: 10.1016/j.biomaterials.2024.122765. Epub 2024 Aug 24.

Abstract

Accurate and early detection of atherosclerosis (AS) is imperative for their effective treatment. However, fluorescence probes for efficient diagnosis of AS often encounter insufficient deep tissue penetration, which hinders the reliable assessment of plaque vulnerability. In this work, a reactive oxygen species (ROS) activated near-infrared (NIR) fluorescence and photoacoustic (FL/PA) dual model probe TPA-QO-B is developed by conjugating two chromophores (TPA-QI and O-OH) and ROS-specific group phenylboronic acid ester. The incorporation of ROS-specific group not only induces blue shift in absorbance, but also inhibits the ICT process of TPA-QO-OH, resulting an ignorable initial FL/PA signal. ROS triggers the convertion of TPA-QO-B to TPA-QO-OH, resulting in the concurrent amplification of FL/PA signal. The exceptional selectivity of TPA-QO-B towards ROS makes it effectively distinguish AS mice from the healthy. The NIR emission can achieve a tissue penetration imaging depth of 0.3 cm. Moreover, its PA signal possesses the capability to penetrate tissues up to a thickness of 0.8 cm, ensuring deep in vivo imaging of AS model mice in early stage. The ROS-triggered FL/PA dual signal amplification strategy improves the accuracy and addresses the deep tissue penetration problem simultaneously, providing a promising tool for in vivo tracking biomarkers in life science and preclinical applications.

摘要

准确和早期检测动脉粥样硬化(AS)对于其有效治疗至关重要。然而,用于有效诊断 AS 的荧光探针通常遇到组织穿透深度不足的问题,这阻碍了斑块脆弱性的可靠评估。在这项工作中,通过将两个生色团(TPA-QI 和 O-OH)和 ROS 特异性基团苯硼酸酯缀合,开发了一种活性氧(ROS)激活的近红外(NIR)荧光和光声(FL/PA)双模式探针 TPA-QO-B。ROS 特异性基团的引入不仅引起吸收的蓝移,而且抑制 TPA-QO-OH 的 ICT 过程,导致初始 FL/PA 信号可以忽略不计。ROS 触发 TPA-QO-B 向 TPA-QO-OH 的转化,从而同时放大 FL/PA 信号。TPA-QO-B 对 ROS 的特殊选择性使其能够有效地将 AS 小鼠与健康小鼠区分开来。NIR 发射能够实现 0.3 cm 的组织穿透成像深度。此外,其 PA 信号具有穿透厚度达 0.8 cm 的组织的能力,确保了早期 AS 模型小鼠的体内深层成像。ROS 触发的 FL/PA 双信号放大策略提高了准确性并解决了深层组织穿透问题,为生命科学和临床前应用中的体内追踪生物标志物提供了一种有前途的工具。

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