Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of Chemistry, School of Chemistry and Molecular Engineering , East China Normal University , Dongchuan Road 500 , Shanghai 200241 , China.
ACS Nano. 2018 Dec 26;12(12):12357-12368. doi: 10.1021/acsnano.8b06322. Epub 2018 Nov 15.
Herein, a single highly selective DNA nanoprobe was designed and created for the real-time imaging and simultaneous quantification of two kinds of biological species using Ca and pH; the molecules were selected as models because of their close relationship with cellular functions and diseases. A Ca fluorescent probe was synthesized and assembled onto a DNA nanostructure together with pH-responsive, inner-reference, and mitochondria-targeted molecules. This nanoprobe with high spatial resolution, together with long-term fluorescent and structural stability, powerfully tracked pH and Ca dynamics at the same localization in mitochondria in response to O-induced oxidative stress and aggregated amyloid β (Aβ) stimulation with a temporal resolution of milliseconds. Using this tool, we discovered that O and Aβ triggered transitory cytoplasmic acidosis and then activated acid-sensing ion channel 1a (ASIC1a) in the mitochondrial membrane, leading to mitochondrial Ca overload and pH abnormalities, which contribute to neuron death. Moreover, psalmotoxin 1 effectively protected against O- and Aβ-induced neuron injury.
本文设计并创建了一种单链高选择性 DNA 纳米探针，用于使用 Ca 和 pH 实时成像和同时定量两种生物物质；选择这些分子作为模型是因为它们与细胞功能和疾病密切相关。合成了一种 Ca 荧光探针，并将其与 pH 响应、内参和线粒体靶向分子一起组装到 DNA 结构上。这种具有高空间分辨率的纳米探针，加上长期荧光和结构稳定性，能够以毫秒级的时间分辨率在同一线粒体定位处有力地跟踪 O 诱导的氧化应激和聚集的淀粉样β（Aβ）刺激下的 pH 和 Ca 动力学。使用这种工具，我们发现 O 和 Aβ触发了短暂的细胞质酸中毒，然后激活了线粒体膜中的酸感应离子通道 1a（ASIC1a），导致线粒体 Ca 超载和 pH 异常，从而导致神经元死亡。此外，psalmotoxin 1 可有效防止 O 和 Aβ诱导的神经元损伤。
