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A graphene oxide nanosensor enables the co-delivery of aptamer and peptide probes for fluorescence imaging of a cascade reaction in apoptotic signaling

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Abstract

Cytochrome c (Cyt c) and caspase-3 are the key mediators in apoptotic signaling. As is known to all, the release of Cyt c from mitochondria is a vital caspase activation pathway and defines the point of no-return in cell apoptosis. However, it has not been reported that any fluorescence imaging tools could allow simultaneous visualization of Cyt c translocation and caspase-3 activation in apoptotic cells. Here, we develop a sensitive nanosensor that holds the capability of imaging of the released Cyt c from the mitochondria and a caspase-3 activation cascade reaction in apoptotic signaling. The nanosensor is constructed by the assembly of a fluorophore (Cy5)-tagged DNA aptamer on graphene nanosheets that have been covalently immobilized with a FAM-labeled peptide. After a spatially selective delivery into the cytoplasm, the Cy5-tagged DNA aptamer assembled on the nanosensor can bind with Cyt c released from the mitochondria to the cytoplasm and dissociate from graphene, triggering a red fluorescence signal. In addition, the caspase-3 activated by the Cyt c released to the cytoplasm can cleave the FAM-labeled peptide and result in a green fluorescence output. The nanosensor exhibits rapid response, high sensitivity and selectivity for in vitro assays, and high contrast imaging of Cyt c and caspase-3 in living cells. It also provides the method for the study of the kinetic relationship between the Cyt c translocation and caspase-3 activation through simultaneous imaging of Cyt c and caspase-3. The developed nanosensor described here will be an efficient and potential platform for apoptosis research.

Graphical abstract: A graphene oxide nanosensor enables the co-delivery of aptamer and peptide probes for fluorescence imaging of a cascade reaction in apoptotic signaling

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Publication details

The article was received on 12 Sep 2017, accepted on 14 Nov 2017 and first published on 15 Nov 2017


Article type: Paper
DOI: 10.1039/C7AN01515A
Citation: Analyst, 2018, Advance Article
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    A graphene oxide nanosensor enables the co-delivery of aptamer and peptide probes for fluorescence imaging of a cascade reaction in apoptotic signaling

    C. Liu, Y. Hu, W. Deng, Q. Pan, J. Yi, T. Chen and X. Chu, Analyst, 2018, Advance Article , DOI: 10.1039/C7AN01515A

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