Zero-Background Small-Molecule Sensors for Near-IR Fluorescent Imaging of Biomacromolecular Targets in Cells
Zero-Background Small-Molecule Sensors for Near-IR Fluorescent Imaging of Biomacromolecular Targets in Cells
复制标题
DOI：
10.1021/acssensors.2c02342
复制
发表时间：
2023-03-03
期刊：
影响因子：
8.9
通讯作者：
Nesterova，Irina V.
中科院分区：
文献类型：
--
作者：
Mohamed，Myar;Klenke，Anastasia K.;Nesterova，Irina V.
在这项研究中，我们报告了一种通用的方法来设计新一代的小分子传感器，产生零背景，但在近红外光谱范围内明亮的荧光后，选择性地与生物分子的目标相互作用。我们发展了一种基于酞菁发色团聚集/解聚的荧光开/关机制。作为一个概念的证明，我们设计，制备和表征的传感器在细胞内可视化的表皮生长因子受体（EGFR）酪氨酸激酶。我们建立了结构/生物利用度相关性，确定了最佳传感器摄取和成像的条件，并在涉及活细胞和固定细胞的广泛治疗选择中证明了结合特异性和应用。该新方法能够实现高对比度成像，并且不需要细胞内化学组装或后处理（即，洗涤）。在这项工作中所展示的一般设计原则可以扩展到其他生物分子目标的传感器和成像剂。
In this study, we report a general approach to the design of a new generation of small-molecule sensors that produce a zero background but are brightly fluorescent in the near-IR spectral range upon selective interaction with a biomolecular target. We developed a fluorescence turn-on/-off mechanism based on the aggregation/deaggregation of phthalocyanine chromophores. As a proof of concept, we designed, prepared, and characterized sensors for in-cell visualization of epidermal growth factor receptor (EGFR) tyrosine kinase. We established a structure/bioavailability correlation, determined conditions for the optimal sensor uptake and imaging, and demonstrated binding specificity and applications over a wide range of treatment options involving live and fixed cells. The new approach enables high-contrast imaging and requires no in-cell chemical assembly or postexposure manipulations (i.e., washes). The general design principles demonstrated in this work can be extended toward sensors and imaging agents for other biomolecular targets.