title: Visualization and Inhibition of Mitochondria-Nuclear Translocation of Apoptosis Inducing Factor by a Graphene Oxide-DNA Nanosensor.
abstract: 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.
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University , Jinan, Shandong 250014, P.R. China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Sun
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University , Jinan, Shandong 250014, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Gao
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University , Jinan, Shandong 250014, P.R. China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University , Jinan, Shandong 250014, P.R. China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Cao
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University , Jinan, Shandong 250014, P.R. China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University , Jinan, Shandong 250014, P.R. China.
authors.forename: Guanwei
authors.initials: G
authors.lastname: Cui
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University , Jinan, Shandong 250014, P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Tong
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University , Jinan, Shandong 250014, P.R. China.
authors.forename: Fengcai
authors.initials: F
authors.lastname: Lei
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University , Jinan, Shandong 250014, P.R. China.
authors.forename: Bo
authors.identifier: 0000-0002-8712-7025
authors.initials: B
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000032:analysis* / Q000737:chemistry; D000067493:Dynamic Light Scattering; D005456:Fluorescent Dyes / Q000737:chemistry; D006108:Graphite / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D049329:Nanostructures / Q000737:chemistry*; D051381:Rats
chemical_list: D051033:Apoptosis Inducing Factor; D005456:Fluorescent Dyes; D008077:Lipoproteins, LDL; C000628730:graphene oxide; C099252:oxidized low density lipoprotein; D006108:Graphite; D004247:DNA