Visualization and Inhibition of Mitochondria-Nuclear Translocation of Apoptosis Inducing Factor by a Graphene Oxide-DNA Nanosensor.

High concentrations of oxidized low density lipoprotein (oxLDL) induce aberrant apoptosis of vascular smooth muscle cells (VSMCs) in atherosclerotic plaques. This apoptosis cannot be blocked completely by the inhibition of caspase, and it eventually potentiates plaque disruption and risk for cardiovascular disease. Given the important role of apoptosis inducing factor (AIF) in caspase-independent apoptosis, here we develop an AIF-targeting nanosensor by the assembly of graphene oxide (GO) nanosheets and dye-labeled DNA hybrid structures. This nanosensor selectively localizes in the cytosol of VSMCs, where it exhibits a "turn-off" fluorescence signal. Under oxLDL stimuli, the release of AIF from mitochondria into cytosol liberates the DNA hybrid structures from the surface of GO and results in a "turn-on" fluorescence signal. This nanosensor is shown to possess rapid response, high sensitivity, and selectivity for AIF that enables real-time imaging of AIF translocation in VSMCs. Using this novel nanosensor, a better assessment of the apoptotic level of VSMCs and a more accurate evaluation of the extent of atherosclerotic lesions can be obtained. More importantly, the abundant binding between DNA hybrid structures and AIF inhibits the translocation of AIF into the nucleus and subsequent apoptosis in VSMCs. This inhibition may help stabilize plaque and reduce the risk of heart attack and stroke.