溶酶体靶向远红光至近红外荧光探针用于监测铁死亡过程中粘度的变化

A Lysosome-Targeted Far-Red to Near-Infrared Fluorescent Probe for Monitoring Viscosity Change During the Ferroptosis Process

阐明病理过程与溶酶体粘度之间的内在关系是一个巨大的挑战.到目前为止,还未有文献报道铁死亡过程中溶酶体粘度的变化情况.在本工作中,设计并合成了一种基于氟硼二吡咯(BODIPY)染料可用于检测粘度的新型远红光至近红外荧光探针FNVP.该探针对粘度变化具有良好的响应能力(λex=600nm,λem=680nm).在磷酸盐缓冲生理盐水(PBS)-甘油体系(1~219 cP)中,探针FNVP在680 nm处的荧光强度约增加50倍.其次,探针具有专一性好、光稳定性强、细胞毒性小等优点,并可用于溶酶体定位及制霉菌素诱导下的细胞粘度监测.最后,利用共聚焦荧光技术,在细胞水平上进行铁死亡过程中的溶酶体粘度成像.这项工作的实施将帮助我们进一步了解铁死亡过程的生物学效应.

Elucidating the intrinsic complex relationship between pathophysiological processes and lysosomal viscosity is a tremendous challenge. So far, the change of lysosomal viscosity during the ferroptosis process has not been reported. In this study, a novel far-red to near-infrared viscosity fluorescent probe(FNVP) was designed and synthesized based on boron dipyrromethene(BODIPY) dye. The probe exhibited excellent responsiveness to viscosity change(λex=600 nm, λem=680nm). In the phosphate buffered saline(PBS)-glycerol system(1~219 cP), the emission intensity of probe FNVP at 680 nm had about a 50-times increase. Furthermore, the probe showed the advantages of high selectivity, remarkable photostability and negligible cytotoxicity. Probe FNVP was lysosome-targetable and could be used for monitoring lysosomal viscosity changes induced by nystatin. Finally, using confocal fluorescence microscopy, lysosome viscosity was imaged during the ferroptosis process at the cellular level. All those will be beneficial to further comprehending the biological effectiveness of ferroptosis.