Mitochondria-Targeted DNA Nanoprobe for Real-Time Imaging and Simultaneous Quantification of Ca2+ and pH in Neurons.

作者：Liu Zhichao; Pei Hao; Zhang Limin; Tian Yang

来源：ACS Nano, 2018.

DOI：10.1021/acsnano.8b06322

Herein, a single highly selective DNA nanoprobe was designed and created for real-time imaging and simultaneous quantification of two kinds of biological species, Ca2+ and pH, which were selected as model molecules because of their close relationship with cellular functions and diseases. A Ca2+ 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 Ca2+ dynamics at the same localization in mitochondria in response to O2*--induced oxidative stress and aggregated amyloid beta (Abeta) stimulation with a temporal resolution of milliseconds. Using this tool, we discovered O2*- and Abeta triggered transitory cytoplasmic acidosis, then activated acid-sensing ion channel 1a (ASIC1a) channel in the mitochondrial membrane, leading to mitochondrial Ca2+ overload and pH abnormal, which contribute to neuron death. Moreover, psalmotoxin 1 effectively protected O2*- and/or Abeta-induced neuron injury.