Ultrasensitive and Selective Detection of a Prognostic Indicator in Early‐Stage Cancer Using Graphene Oxide and Carbon Nanotubes

Abstract

Cyclin A2 is a prognostic indicator in early‐stage cancer. However, since most of peptide‐protein bindings do not produce an easily measurable output signal, this severely hinders homogeneous detection of protein using peptide as detection probe. Cyclin A2 can be detected as low as 0.6 μM using a well‐known p21(WAF‐1) consensus senquence for a specific cyclin A2 binding motif, which is incorporated into a Tb3+ chelating macrocycle by chemical modification at the N‐terminus of CMB. Herein, a simple, ultra‐sensitive, and selective signal‐on fluorescence assay is developed for detection of a prognostic indicator in early‐stage cancer, cyclin A2. Graphene oxide (GO) is even superior to SWNTs for cyclin A2 detection. The direct detection limit using graphene oxide is 0.5 nM, 10‐fold better than using SWNTs, and 1200‐fold better than the latest reported value of 0.6 μM using the Tb3+ chelating macrocycle modified p21(WAF‐1) peptide.

Sensitive and Rapid Screening of T4 Polynucleotide Kinase Activity and Inhibition Based on Coupled Exonuclease Reaction and Graphene Oxide Platform

“…The fact is attributed to the strong adsorption of the ssDNA on the GO surface and the super fluorescence quenching ability of GO originated from the effective FRET between dye and GO. 33 While, as a comparison, 80% fluorescence still remained when dsDNA-FAM was mixed with GO under the same experimental conditions ( Figure 1B). It is mainly due to the weak and unstable adsorption of dsDNA-FAM on the GO surface, which inhibited the FRET between the dye and GO.…”

Synergistic pH effect for reversible shuttling aptamer-based biosensors between graphene oxide and target molecules

“…[5][6][7][8] For example, GO can effectively quench adsorbed fluorophores. These properties have been used to make highly sensitive fluorescent biosensors for metal ions, [9][10][11] small molecules, [12][13][14][15][16] proteins, [17][18][19][20] and DNA. 10,18,[21][22][23][24][25][26] For example, mixing a fluorescently labeled aptamer with GO resulted in quenched fluorescence.…”

New Horizons for Diagnostics and Therapeutic Applications of Graphene and Graphene Oxide

“…The specifi c peptide and protein interaction provides another molecular recognition for protein sensing, and this strategy eliminates the need for antibodies mentioned above and has more generality. [ 39 ] In vitro screen techniques produce a large number of engineering polypeptide recognition elements that tightly and specifi cally bind to a wide range of biomarker proteins. Our group reported the fi rst graphene-based peptide sensor for detection of cyclin A 2 protein through fl uorescence quenching-recovery method.…”

“…Our group reported the fi rst graphene-based peptide sensor for detection of cyclin A 2 protein through fl uorescence quenching-recovery method. [ 39 ] Cyclin A 2 is a prognostic indicator in early-stage cancers and has been reported overexpressed in many types of cancers including breast cancer, liver cancer, lung cancer, soft tissue sarcoma, leukemia, and lymphoma. [ 54 ] It is associated with the proliferation rate of these disorders and is a promising anti-cancer target by targeting the cyclin A 2 substrate recruitment element called the cyclin binding groove (CBG).…”

“…It was 10-fold better than using SWNTs as quencher, and 1200-fold better than the latest reported value of 0.6 μ M using Tb 3 + chelating macrocycle modifi ed p21 (WAF-1) peptide. [ 39 ] Zhang et al . also developed a graphene-based biosensing platform using peptides as probe biomolecules, and demonstrated its feasibility in the application of real-time monitoring of protease activity with a detection limit of thrombin of 2 nM.…”