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

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.