研究动态
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多功能荧光探针用于同时检测ONOO-,粘度和极性,并在铁死亡和癌症模型中应用。

Multifunctional Fluorescent Probe for Simultaneous Detection of ONOO-, Viscosity, and Polarity and Its Application in Ferroptosis and Cancer Models.

发表日期:2023 Mar 20
作者: Li Fan, Qianqian Yang, Qi Zan, Kunyi Zhao, Wenjing Lu, Xu Wang, Yu Wang, Shaomin Shuang, Chuan Dong
来源: Environmental Technology & Innovation

摘要:

细胞内的过氧亚硝酸根离子(ONOO-)和微环境(如粘度和极性)在维持氧化还原平衡、调节扩散、运输和信号转导等方面在活细胞中起着重要作用。这些因素的异常常常与各种生理/病理过程密切相关。然而,由于缺乏适合的探针,迄今为止尚未实现在铁死亡和癌症模型中同时可视化ONOO-、粘度和极性。为了满足迫切需求,我们提出了一种多功能近红外(NIR)荧光探针MQA-P,用于在线粒体内同时检测ONOO-、粘度和极性。该探针对ONOO-表现出显著的打开响应,远红发射约为645nm,并对NIR通道中的粘度/极性非常敏感,λem > 704nm。在MQA-P的帮助下,我们首次发现,由erastin诱导的铁死亡伴随着ONOO-的显著上调和粘度的增加(或极性的降低)。此外,ONOO-、粘度和极性的同步使用不仅在细胞/组织水平上,而且在肿瘤小鼠模型中成功实现了癌症诊断。与仅检测一种因素相比,这种多标记物的同时检测为追踪铁死亡相关的病理过程和癌症诊断提供了更敏感、可靠的方法/工具,在临床前研究、医学诊断和影像引导手术方面具有巨大的潜力。
Intracellular peroxynitrite anions (ONOO-) and microenvironments (such as viscosity and polarity) play an important role in maintaining redox homeostasis, regulating diffusion, transportation, and signal transduction in living cells. The abnormality of these factors is often closely related to various physiological/pathological processes. However, owing to the lack of suitable probes, the simultaneous visualization of ONOO-, viscosity, and polarity in ferroptosis and cancer models has not been achieved. To meet urgent needs, we presented a multifunctional near-infrared (NIR) fluorescent probe, named MQA-P, for simultaneously detecting ONOO-, viscosity, and polarity within mitochondria. The probe exhibited a remarkable turn-on response to ONOO- with the far-red emission of about 645 nm and was highly sensitive to viscosity/polarity in the NIR channel with λem > 704 nm. Facilitated by MQA-P, for the first time, we revealed that erastin-induced ferroptosis was accompanied by a significant upregulation of ONOO- and an increase of viscosity (or decrease of polarity) at the same time. Moreover, the concurrent use of ONOO-, viscosity, and polarity for the diagnosis of cancer has been successfully achieved not only at cell/tissue levels but also in tumor mice models. Compared with detecting only one factor, this simultaneous detection of multimarkers provides a more sensitive and reliable method/tool for tracking ferroptosis-related pathological processes and cancer diagnosis, holding great potential in preclinical research, medical diagnosis, and imaging-guided surgery.