Mesh : Fluorescent Dyes / chemistry Humans Artemisinins / pharmacology chemistry Boron Compounds / chemistry Ferroptosis / drug effects Animals Mice Sulfhydryl Compounds / chemistry Optical Imaging Reactive Oxygen Species / metabolism

来  源:   DOI:10.1021/acs.analchem.4c02431

Abstract:
The occurrence and development of diseases are accompanied by abnormal activity or concentration of biomarkers in cells, tissues, and blood. However, the insufficient sensitivity and accuracy of the available fluorescence probes hinder the precise monitoring of associated indexes in biological systems, which is generally due to the high probe intrinsic fluorescence and false-negative signal caused by the reactive oxygen species (ROS)-induced probe decomposition. To resolve these problems, we have engineered a ROS-stable, meso-carboxylate boron dipyrromethene (BODIPY)-based fluorescent probe, which displays quite a low background fluorescence due to the doubly quenched intrinsic fluorescence by a combined strategy of the photoinduced electron transfer (PET) effect and \"ester-to-carboxylate\" conversion. The probe achieved a high S/N ratio with ultrasensitivity and good selectivity toward biothiols, endowing its fast detection capability toward the biothiol level in 200×-diluted plasma samples. Using this probe, we achieved remarkable distinguishing of liver injury plasma from normal plasma even at 80× dilution. Moreover, owing to its good stability toward ROS, the probe was successfully employed for high-fidelity imaging of the negative fluctuation of the biothiol level in nonsmall-cell lung cancer (NSCLC) during dihydroartemisinin-induced ferroptosis. This delicate design of suppressing intrinsic fluorescence reveals insights into enhancing the sensitivity and accuracy of fluorescent probes toward the detection and imaging of biomarkers in the occurrence and development of diseases.
摘要:
疾病的发生发展伴随着细胞内生物标志物的异常活性或浓度,组织,还有血.然而,可用荧光探针的灵敏度和准确性不足阻碍了对生物系统中相关指标的精确监测,这通常是由于高探针固有荧光和假阴性信号引起的活性氧(ROS)诱导的探针分解。为了解决这些问题,我们设计了一个ROS稳定的,内消旋羧酸硼二吡咯亚甲基(BODIPY)基荧光探针,由于光诱导电子转移(PET)效应和“酯到羧酸酯”转换的组合策略,由于双重猝灭的固有荧光,因此显示出相当低的背景荧光。该探针实现了高S/N比,具有超灵敏度和对生物硫醇的良好选择性,赋予其对200倍稀释血浆样品中生物硫醇水平的快速检测能力。使用这个探测器,即使在80倍稀释时,我们也能显着区分肝损伤血浆和正常血浆。此外,由于其对ROS的良好稳定性,该探针成功用于双氢青蒿素诱导的铁凋亡期间非小细胞肺癌(NSCLC)生物硫醇水平负波动的高保真成像.这种抑制固有荧光的精巧设计揭示了提高荧光探针在疾病发生和发展中对生物标志物的检测和成像的灵敏度和准确性的见解。
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