Institute of Intelligent Machines, Chinese Academy of Sciences, Hefei, Anhui, 230031, China.
Department of Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China.
Angew Chem Int Ed Engl. 2019 May 20;58(21):7087-7091. doi: 10.1002/anie.201903005. Epub 2019 Apr 10.
The dynamics of DNA and RNA structures in live cells are important for understanding cell behaviors, such as transcription activity, protein expression, cell apoptosis, and hereditary disease, but are challenging to monitor in live organisms in real time. The difficulty is largely due to the lack of photostable imaging probes that can distinguish between DNA and RNA, and more importantly, are capable of crossing multiple membrane barriers ranging from the cell/organelle to the tissue/organ level. We report the discovery of a cationic carbon quantum dot (cQD) probe that emits spectrally distinguishable fluorescence upon binding with double-stranded DNA and single-stranded RNA in live cells, thereby enabling real-time monitoring of DNA and RNA localization and motion. A surprising finding is that the probe can penetrate through various types of biological barriers in vitro and in vivo. Combined with standard and super-resolution microscopy, photostable cQDs allow time-lapse imaging of chromatin and nucleoli during cell division and Caenorhabditis elegans (C. elegans) growth.
活细胞中 DNA 和 RNA 结构的动态变化对于理解细胞行为(如转录活性、蛋白质表达、细胞凋亡和遗传性疾病)非常重要,但实时监测活生物体中的这些变化具有挑战性。这种困难主要归因于缺乏光稳定的成像探针,这些探针能够区分 DNA 和 RNA,更重要的是,能够跨越从细胞/细胞器到组织/器官水平的多种膜屏障。我们报告了一种阳离子碳量子点(cQD)探针的发现,该探针在与活细胞中的双链 DNA 和单链 RNA 结合时会发出光谱上可区分的荧光,从而能够实时监测 DNA 和 RNA 的定位和运动。一个令人惊讶的发现是,该探针可以穿透体外和体内的各种类型的生物屏障。结合标准和超分辨率显微镜,光稳定的 cQD 可以在细胞分裂和秀丽隐杆线虫(C. elegans)生长过程中对染色质和核仁进行延时成像。