Fluorescent Probes for Biological Species and Microenvironments:from Rational Design to Bioimaging Applications

生物物种和微环境的荧光探针:从理性设计到生物成像应用

主讲人：文正

https://doi.org/10.1021/acs.accounts.2c00643

Acc. Chem. Res. 2023, 56, 258−269

ABSTRACT:

         Some important biological species and micro-environments maintain a complex and delicate dynamic balance in life systems, participating in the regulation of various physiological processes and playing indispensable roles in maintaining the healthy development of living bodies. Disruption of their homeostasis in living organisms can cause various diseases and even death. Therefore, real time monitoring of these biological species and microenvironments during different physiological and pathological processes is of great significance. Fluorescent-probe- based techniques have been recognized as one of the most powerful tools for real time imaging in biological samples. In this Account, we introduce the representative works from our group in the field of fluorescent probes for biological imaging capable of detecting metal ions, small bioactive molecules, and the microenvironment. The design strategies of small molecule fluorescent probes and their applications in biological imaging will be discussed. By regulating the design strategy and mechanism (e.g., ICT, PeT, and FRET) of the electronic and spectral characteristics of the fluorescent platforms, these chemical probes show high selectivity and diverse functions, which can be used for imaging of various physiological and pathological processes. Through the exploration of the rational response mechanism and design strategy, combined with a variety of imaging techniques, such as super-resolution imaging, photoacoustic (PA) imaging, etc., we have realized multimode imaging of the important biological analytes from the subcellular level to the in vivo level, which provides powerful means to study the physiological and pathological functions of these species and microenvironments. This Account aims to offer insights and inspiration for the development of novel fluorescent probes for biological imaging, which could provide powerful tools for the study of chemical biology. Overall, we represent a series of turn-on/turn-off/ratiometric fluorescent/PA probes to visually and dynamically trace biological species and microenvironments in cells and even in vivo that seek higher resolution and depth molecular imaging to improve diagnostic methods and clarify new discoveries related to chemical biology. Our future efforts will be devoted to developing multiorganelle targeted fluorescent probes to study the mechanism of subcellular organelle interaction and employing various dual-mode probes of NIR II and PA imaging to investigate the development of related diseases and treat the related diseases at subcellular and in vivo levels.

摘要：

   一些重要的生物物种和微环境在生命系统中维持着复杂而微妙的动态平衡，参与调节各种生理过程，对维持生物体的健康发育起着不可或缺的作用。在生物体中破坏它们的体内平衡会导致各种疾病甚至死亡。因此，实时监测这些生物物种和微环境在不同的生理和病理过程中具有重要意义。基于荧光探针的技术已被认为是生物样品实时成像最强大的工具之一。本文介绍了本课组在生物成像荧光探针领域的代表性研究成果，这些荧光探针能够检测金属离子、小生物活性分子和微环境。讨论了小分子荧光探针的设计策略及其在生物成像中的应用。这些化学探针通过调控荧光平台电子和光谱特性的设计策略和机制(如ICT、PeT和FRET)，显示出高选择性和多样化的功能，可用于各种生理和病理过程的成像。通过对合理反应机制和设计策略的探索，结合超分辨率成像、光声成像(PA)等多种成像技术，实现了重要生物分析物从亚细胞水平到体内水平的多模式成像，为研究这些物种及其微环境的生理病理功能提供了有力手段。本文旨在为新型生物成像荧光探针的开发提供见解和灵感，为化学生物学的研究提供有力的工具。总的来说，我们提出了一系列开启/关闭/比率荧光/PA探针，以视觉和动态地追踪细胞内甚至体内的生物物种和微环境，寻求更高分辨率和深度的分子成像，以改进诊断方法并阐明与化学生物学相关的新发现。我们未来将致力于开发多细胞器靶向荧光探针来研究亚细胞细胞器相互作用的机制，并利用各种近红外成像和PA成像双模探针在亚细胞和体内水平上研究相关疾病的发生发展和治疗相关疾病。