新型近红外荧光探针成像细胞肺纤维化过程粘度变化

A Novel Near-infrared Fluorescent Probe for Visualizing Viscosity Fluxes in Live Cells and Idiopathic Pulmonary Fibrosis

肺纤维化是一种致命疾病,患病率不断上升。肺纤维化的非放射性和无创性早期诊断可以改善预后,但却是艰巨的挑战。粘度的异常是肺纤维化的典型微环境特征。最近,粘度的精准可视化检测引起了人们的广泛兴趣。然而,由于其特性复杂,直接观察生物系统中的粘度仍然是一个巨大的挑战。线粒体粘度波动与肺纤维化、糖尿病、神经退行性疾病、癌症等多种疾病有关。在这里,报告了一种新型小分子荧光探针NIR-V-BR,用于检测线粒体粘度变化。NIR-V-BR对粘度变化具有近红外发射、优异的水溶性、良好的光稳定性、良好的膜通透性和低细胞毒性。共定位实验表明NIR-V-BR探针具有良好的线粒体靶向能力。NIR-V-BR成功应用于成像活细胞线粒体中粘度变化。最重要的是,NIR-V-BR探针荧光成像实验表明肺纤维化细胞中粘度水平升高。这些结果表明,NIR-V-BR将为生物医学诊断和成像应用提供新的机会。

Pulmonary fibrosis is a fatal disease with increasing prevalence.Nonradioactive and noninvasive diagnosis of pulmonary fibrosis at an early stage can improve the prognosis but represents a daunting challenge.Viscosity is a typical microenvironmental feature of pulmonary fibrosis.Recently,precise visualization of viscosity has begun to stimulate more and more interest.However,owing to the complicated character,it is still a huge challenge to directly observe viscosity in living systems.Mitochondria viscosity fluctuation is related to various diseases such as pulmonary fibrosis,diabetes,neurodegenerative diseases,and cancer.Herein,a novel viscosity probes NIR-V-BR was developed for monitoring the viscosity change of mitochondria.NIR-V-BR possessed a highly sensitive response toward viscosity change with near-infrared emission,excellent water solubility,good photostability,favorable membrane permeabilization,and low cytotoxicity.Colocalization study proved that NIR-V-BR probe exhibited good mitochondrion-targeting ability.NIR-V-BR is used for imaging of viscosity changes in mitochondrion of living cells.Most importantly,fluorescence imaging experiments with NIR-V-BR probe revealed that the level of intracellular viscosity increases in the pulmonary fibrosis cells.These results suggest that NIR-V-BR would provide new opportunities for biomedical diagnosis and imaging applications.