Zero-Background Small-Molecule Sensors for Near-IR Fluorescent Imaging of Biomacromolecular Targets in Cells,ACS Sensors

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Zero-Background Small-Molecule Sensors for Near-IR Fluorescent Imaging of Biomacromolecular Targets in Cells
ACS Sensors ( IF 8.2 ) Pub Date : 2023-03-03 , DOI: 10.1021/acssensors.2c02342
Myar Mohamed ₁ , Anastasia K Klenke ₁ , Maksim V Anokhin ₁ , Harouna Amadou ₁ , Paige J Bothwell ₁ , Brigid Conroy ₁ , Evgueni E Nesterov ₁ , Irina V Nesterova ₁

Affiliation

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.

中文翻译：

用于细胞中生物大分子靶标的近红外荧光成像的零背景小分子传感器

在这项研究中，我们报告了设计新一代小分子传感器的通用方法，该传感器产生零背景，但在与生物分子靶标选择性相互作用时在近红外光谱范围内发出明亮的荧光。我们开发了一种基于酞菁发色团聚集/解聚的荧光开启/关闭机制。作为概念验证，我们设计、制备并表征了用于表皮生长因子受体 (EGFR) 酪氨酸激酶细胞内可视化的传感器。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，并证明了在涉及活细胞和固定细胞的各种治疗方案中的结合特异性和应用。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曝光后操作（即清洗）。这项工作中展示的一般设计原理可以扩展到其他生物分子目标的传感器和成像剂。

更新日期：2023-03-03

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