Mitochondria-Targeted DNA Nanoprobe for Real-Time Imaging and Simultaneous Quantification of Ca2+ 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 Ca2+ and pH; the molecules were selected as models 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 O-2(center dot-)-induced oxidative stress and aggregated amyloid beta (A beta) stimulation with a temporal resolution of milliseconds. Using this tool, we discovered that O-2(center dot-) and A beta triggered transitory cytoplasmic acidosis and then activated acid-sensing ion channel la (ASIC1a) in the mitochondrial membrane, leading to mitochondrial Ca2+ overload and pH abnormalities, which contribute to neuron death. Moreover, psalmotoxin 1 effectively protected against O-2(center dot-) - and A beta-induced neuron injury.