Copper (II) oxide nanozyme based electrochemical cytosensor for high sensitive detection of circulating tumor cells in breast cancer

Abstract An ultrasensitive electrochemical detection method was developed to detect circulating tumor cells (CTCs) by using reduced graphene oxide/gold nanoparticles composites (rGO/AuNPs composites) as a support material with CuO nanozyme as a catalyst. MCF-7 circulating tumor cells were detected by an electrochemical cytosensor with effective surface recognition between specific mucin 1 protein (MUC-1) over-expressed on the MCF-7 cell membranes and MUC-1 aptamer. The CuO nanozyme is used as a signal-amplifying nanoprobe in an ultrasensitive electrochemical cytosensor to detect CTCs for the first time. Under the optimized experimental conditions, the proposed cytosensor exhibited significant analytical performance for the determination of MCF-7 circulating tumor cells. A wide detection range from 50 to 7 × 103 cells mL− 1 with a detection limit as low as 27 cells mL− 1 was reached on the condition of acceptable selectivity and reproducibility. Furthermore, the cytosensor can easily distinguish CTCs from the real serum sample due to the specific combination of MUC-1 and MUC-1 aptamer.

[1]  X. Xia,et al.  Pure Pyridinic Nitrogen‐Doped Single‐Layer Graphene Catalyzes Two‐Electron Transfer Process of Oxygen Reduction Reaction , 2016 .

[2]  R. Ghossein,et al.  Molecular detection and characterisation of circulating tumour cells and micrometastases in solid tumours. , 2000, European journal of cancer.

[3]  Winfried Wiegraebe,et al.  Detection of functional haematopoietic stem cell niche using real-time imaging , 2009, Nature.

[4]  T. Pal,et al.  Soft template induced phase selective synthesis of Fe2O3 nanomagnets: one step towards peroxidase-mimic activity allowing colorimetric sensing of thioglycolic acid , 2016 .

[5]  Pranjal Chandra,et al.  An amperometric nanobiosensor using a biocompatible conjugate for early detection of metastatic cancer cells in biological fluid. , 2016, Biosensors & bioelectronics.

[6]  Shuming Nie,et al.  Integrated Nanozymes with Nanoscale Proximity for in Vivo Neurochemical Monitoring in Living Brains. , 2016, Analytical chemistry.

[7]  Xiaoyu Wang,et al.  Nanozymes in bionanotechnology: from sensing to therapeutics and beyond , 2016 .

[8]  X. Qu,et al.  Highly sensitive electrochemiluminescent cytosensing using carbon nanodot@Ag hybrid material and graphene for dual signal amplification. , 2013, Chemical communications.

[9]  M. Baghayeri,et al.  A simple hydrogen peroxide biosensor based on a novel electro-magnetic poly(p-phenylenediamine)@Fe3O4 nanocomposite. , 2014, Biosensors & bioelectronics.

[10]  X. Qu,et al.  How functional groups influence the ROS generation and cytotoxicity of graphene quantum dots. , 2017, Chemical communications.

[11]  E. Wang,et al.  Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes. , 2013, Chemical Society reviews.

[12]  Wei Chen,et al.  Self-cascade reaction catalyzed by CuO nanoparticle-based dual-functional enzyme mimics. , 2017, Biosensors & bioelectronics.

[13]  Nitin Kumar,et al.  Colorimetric sensing of malathion using palladium-gold bimetallic nanozyme. , 2017, Biosensors & bioelectronics.

[14]  Jinghua Yu,et al.  CuO-induced signal amplification strategy for multiplexed photoelectrochemical immunosensing using CdS sensitized ZnO nanotubes arrays as photoactive material and AuPd alloy nanoparticles as electron sink. , 2015, Biosensors & bioelectronics.

[15]  X. Qu,et al.  A graphene functionalized electrochemical aptasensor for selective label-free detection of cancer cells. , 2011, Biomaterials.

[16]  Maurizio Prato,et al.  Organic functionalization of graphene in dispersions. , 2013, Accounts of chemical research.

[17]  Fake Li,et al.  Label-free and high-sensitive detection of human breast cancer cells by aptamer-based leaky surface acoustic wave biosensor array. , 2014, Biosensors & bioelectronics.

[18]  Song Zhang,et al.  A novel aptasensor based on MUC-1 conjugated CNSs for ultrasensitive detection of tumor cells. , 2014, The Analyst.

[19]  Da Huo,et al.  Functional Nucleic Acid Probe for Parallel Monitoring K(+) and Protoporphyrin IX in Living Organisms. , 2016, Analytical chemistry.

[20]  Yu Zhang,et al.  Prussian Blue Nanoparticles as Multienzyme Mimetics and Reactive Oxygen Species Scavengers. , 2016, Journal of the American Chemical Society.

[21]  X. Qu,et al.  Ultrasensitive Telomerase Activity Detection in Circulating Tumor Cells Based on DNA Metallization and Sharp Solid‐State Electrochemical Techniques , 2014 .

[22]  M. Lacroix,et al.  Significance, detection and markers of disseminated breast cancer cells. , 2006, Endocrine-related cancer.

[23]  Xiaoli Zhang,et al.  Signal amplification based on DNA hybridization-dehybridization reaction on the surface of magnet submicrobeads for ultrasensitive DNA detection. , 2012, The Analyst.

[24]  Qian Wang,et al.  Monitoring of Heparin Activity in Live Rats Using Metal-Organic Framework Nanosheets as Peroxidase Mimics. , 2017, Analytical chemistry.

[25]  R Paredes-Aguilera,et al.  Flow cytometric analysis of cell‐surface and intracellular antigens in the diagnosis of acute leukemia , 2001, American journal of hematology.

[26]  Jie Huang,et al.  Nanocomposites of size-controlled gold nanoparticles and graphene oxide: formation and applications in SERS and catalysis. , 2010, Nanoscale.

[27]  Guoqiang Sun,et al.  An aptasensor for sensitive detection of human breast cancer cells by using porous GO/Au composites and porous PtFe alloy as effective sensing platform and signal amplification labels. , 2013, Analytica chimica acta.

[28]  A. Perkins,et al.  Anti-MUC1 aptamers: radiolabelling with (99m)Tc and biodistribution in MCF-7 tumour-bearing mice. , 2009, Nuclear medicine and biology.

[29]  A. Wu,et al.  Current detection technologies for circulating tumor cells. , 2017, Chemical Society reviews.

[30]  Kang Wang,et al.  Exploration of the Copper Active Sites in Electrooxidation of Glucose on a Copper/Nitrogen Doped Graphene Nanocomposite , 2016 .

[31]  Arben Merkoçi,et al.  Rapid identification and quantification of tumor cells using an electrocatalytic method based on gold nanoparticles. , 2009, Analytical chemistry.

[32]  Xiaojun Zhang,et al.  Preparation of CuO-Nanoparticle-Modified Electrode and Its Application in the Determination of Rutin , 2009 .

[33]  P. Carli,et al.  Circulating and Disseminated Tumor Cells in the Clinical Management of Breast Cancer Patients: Unanswered Questions , 2009, Oncology.

[34]  Shuming Nie,et al.  Surface-Enhanced Raman Scattering Active Gold Nanoparticles with Enzyme-Mimicking Activities for Measuring Glucose and Lactate in Living Tissues. , 2017, ACS nano.

[35]  W. Lu,et al.  Improved synthesis of graphene oxide. , 2010, ACS nano.

[36]  Shaojun Guo,et al.  Graphene nanosheet: synthesis, molecular engineering, thin film, hybrids, and energy and analytical applications. , 2011, Chemical Society reviews.

[37]  David E. Williams,et al.  Point of care diagnostics: status and future. , 2012, Analytical chemistry.

[38]  Jun‐Jie Zhu,et al.  Robust nonenzymatic hybrid nanoelectrocatalysts for signal amplification toward ultrasensitive electrochemical cytosensing. , 2014, Journal of the American Chemical Society.

[39]  R. Christopherson,et al.  Immunophenotyping of leukemias using a cluster of differentiation antibody microarray. , 2001, Cancer research.

[40]  Itamar Willner,et al.  Diagnosing the miR-141 prostate cancer biomarker using nucleic acid-functionalized CdSe/ZnS QDs and telomerase† †Electronic supplementary information (ESI) available: Optimization of detection conditions and tabulation of data in Fig. 3. See DOI: 10.1039/c4sc02104e1 Click here for additional data fi , 2014, Chemical science.

[41]  Erkang Wang,et al.  Fe3O4 magnetic nanoparticles as peroxidase mimetics and their applications in H2O2 and glucose detection. , 2008, Analytical chemistry.

[42]  R. Weissleder,et al.  Imaging in the era of molecular oncology , 2008, Nature.

[43]  M. Pumera,et al.  Electrochemistry of graphene and related materials. , 2014, Chemical reviews.

[44]  Carole Rossi,et al.  High‐Energy Al/CuO Nanocomposites Obtained by DNA‐Directed Assembly , 2012 .

[45]  Yaofang Hu,et al.  Label-free electrochemical impedance spectroscopy biosensor for direct detection of cancer cells based on the interaction between carbohydrate and lectin. , 2013, Biosensors & bioelectronics.

[46]  Yang Liu,et al.  Multienzyme decorated polysaccharide amplified electrogenerated chemiluminescence biosensor for cytosensing and cell surface carbohydrate profiling. , 2017, Biosensors & bioelectronics.

[47]  Xiaogang Qu,et al.  Antibacterial applications of graphene-based nanomaterials: Recent achievements and challenges. , 2016, Advanced drug delivery reviews.

[48]  Xiaoping Shen,et al.  Graphene–inorganic nanocomposites , 2012 .

[49]  Haowen Huang,et al.  Peroxidase-Like Activity of Ethylene Diamine Tetraacetic Acid and Its Application for Ultrasensitive Detection of Tumor Biomarkers and Circular Tumor Cells. , 2017, Analytical chemistry.

[50]  Li-Juan Tang,et al.  Aptamer-aided target capturing with biocatalytic metal deposition: an electrochemical platform for sensitive detection of cancer cells. , 2013, The Analyst.

[51]  X. Xia,et al.  Copper-Nitrogen-Doped Graphene Hybrid as an Electrochemical Sensing Platform for Distinguishing DNA Bases. , 2017, Analytical chemistry.

[52]  Jens Ducrée,et al.  Label-free impedance detection of cancer cells from whole blood on an integrated centrifugal microfluidic platform. , 2015, Biosensors & bioelectronics.

[53]  B. Ye,et al.  Enzyme-free detection of sequence-specific microRNAs based on nanoparticle-assisted signal amplification strategy. , 2016, Biosensors & bioelectronics.

[54]  Hui Zhu,et al.  Sensitive electrochemical sensor for hydrogen peroxide using Fe3O4 magnetic nanoparticles as a mimic for peroxidase , 2011 .

[55]  X. Qu,et al.  Cancer biomarker detection: recent achievements and challenges. , 2015, Chemical Society reviews.

[56]  Hongtao Yu,et al.  Interface engineering catalytic graphene for smart colorimetric biosensing. , 2012, ACS nano.

[57]  Genxi Li,et al.  Sensitive detection of human breast cancer cells based on aptamer-cell-aptamer sandwich architecture. , 2013, Analytica chimica acta.