Electrochemical aptasensor for the detection of vascular endothelial growth factor（VEGF） based on DNA-templated Ag/Pt bimetallic nanoclusters

Abstract In this paper, the DNA-templated Ag/Pt bimetallic nanoclusters were successfully synthesized using an optimized synthetic scheme. The obtained DNA-Ag/Pt NCs have an ultrasmall particle size and excellent distribution. The DNA-Ag/Pt NCs show intrinsic peroxidase-mimicking activity and can effectively catalyze the H 2 O 2 -mediated oxidation of a substrate, 3,3′,5,5′-tetramethylbenzidine (TMB), to produce a blue colored product. Based on this specific property, we employed the aptamer of VEGF to design a label-free electrochemical biosensor for VEGF detection. Under the optimized experimental conditions, a linear range from 6.0 pmol/L to 20 pmol/L was obtained with a detection limit of 4.6 pmol/L. The proposed biosensor demonstrated its high specificity for VEGF and could directly detect the VEGF concentration in human serum samples of breast cancer patients with satisfactory results. This novel electrochemical aptasensor was simple and convenient to use and was cost-effective and label-free in design, and would hold potential applications in medical diagnosis and treatment.

[1]  Feng Li,et al.  Enzyme-free and label-free ultrasensitive electrochemical detection of DNA and adenosine triphosphate by dendritic DNA concatamer-based signal amplification. , 2014, Biosensors & bioelectronics.

[2]  G. Wulff,et al.  Enzyme-like catalysis by molecularly imprinted polymers. , 2002, Chemical reviews.

[3]  Haiyan Cao,et al.  Peroxidase-like activity of chitosan stabilized silver nanoparticles for visual and colorimetric detection of glucose. , 2012, The Analyst.

[4]  Guonan Chen,et al.  Irregular-shaped platinum nanoparticles as peroxidase mimics for highly efficient colorimetric immunoassay. , 2013, Analytica chimica acta.

[5]  Guonan Chen,et al.  One-pot synthesized DNA-templated Ag/Pt bimetallic nanoclusters as peroxidase mimics for colorimetric detection of thrombin. , 2014, Chemical communications.

[6]  Seon Joo Park,et al.  A high-performance VEGF aptamer functionalized polypyrrole nanotube biosensor. , 2010, Biomaterials.

[7]  F. Calzetti,et al.  On the detection of neutrophil-derived vascular endothelial growth factor (VEGF). , 1999, Journal of immunological methods.

[8]  Zhuwu Lv,et al.  A New Electrochemical Aptasensor for the Analysis of the Vascular Endothelial Growth Factor , 2014, Journal of immunoassay & immunochemistry.

[9]  Abdullah M. Asiri,et al.  Ultrathin graphitic carbon nitride nanosheets: a novel peroxidase mimetic, Fe doping-mediated catalytic performance enhancement and application to rapid, highly sensitive optical detection of glucose. , 2013, Nanoscale.

[10]  Wei-Wei Zhao,et al.  Double-probe signal enhancing strategy for toxin aptasensing based on rolling circle amplification. , 2012, Biosensors & bioelectronics.

[11]  Moon-Ho Jo,et al.  Electrical detection of VEGFs for cancer diagnoses using anti-vascular endotherial growth factor aptamer-modified Si nanowire FETs. , 2009, Biosensors & bioelectronics.

[12]  Shihua Wang,et al.  A fluorescent aptasensor based on DNA-scaffolded silver-nanocluster for ochratoxin A detection. , 2014, Biosensors & bioelectronics.

[13]  Yoshio Suzuki,et al.  Development of a Fluorescent Peptide for the Detection of Vascular Endothelial Growth Factor (VEGF) , 2009, Chembiochem : a European journal of chemical biology.

[14]  H. Joensuu,et al.  Leukocytes and platelets of patients with cancer contain high levels of vascular endothelial growth factor. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[15]  F. Di Raimondo,et al.  Angiogenic factors in multiple myeloma: higher levels in bone marrow than in peripheral blood. , 2000, Haematologica.

[16]  Jiechao Ge,et al.  A novel glucose colorimetric sensor based on intrinsic peroxidase-like activity of C60-carboxyfullerenes. , 2013, Biosensors & bioelectronics.

[17]  Huzhi Zheng,et al.  Analytical and environmental applications of nanoparticles as enzyme mimetics , 2012 .

[18]  Xiaogang Qu,et al.  Graphene Oxide: Intrinsic Peroxidase Catalytic Activity and Its Application to Glucose Detection , 2010, Advanced materials.

[19]  W. Carney,et al.  TIMP-1 and VEGF-165 serum concentration during first-line therapy of ovarian cancer patients , 2010, BMC Cancer.

[20]  Wei Sun,et al.  Electrochemical deoxyribonucleic acid biosensor based on carboxyl functionalized graphene oxide and poly-L-lysine modified electrode for the detection of tlh gene sequence related to vibrio parahaemolyticus. , 2012, Analytica chimica acta.

[21]  Qinlong Wang,et al.  Carbon nanodots as peroxidase mimetics and their applications to glucose detection. , 2011, Chemical communications.

[22]  M. Famulok,et al.  Nucleic acid aptamers-from selection in vitro to applications in vivo. , 2000, Accounts of chemical research.

[23]  P. Carmeliet,et al.  VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection , 2004, BioEssays : news and reviews in molecular, cellular and developmental biology.

[24]  Z. Rahman,et al.  Graphene oxide-Fe3O4 magnetic nanocomposites with peroxidase-like activity for colorimetric detection of glucose. , 2012, Nanoscale.

[25]  Chunhai Fan,et al.  Catalytic gold nanoparticles for nanoplasmonic detection of DNA hybridization. , 2011, Angewandte Chemie.

[26]  Inhibited aptazyme-based catalytic molecular beacon for amplified detection of adenosine , 2014 .

[27]  Georg Breier,et al.  Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo , 1992, Nature.

[28]  Ming Yan,et al.  Homogeneously ultrasensitive electrochemical detection of adenosine triphosphate based on multiple signal amplification strategy. , 2014, Biosensors & bioelectronics.

[29]  Eun Jeong Cho,et al.  Applications of aptamers as sensors. , 2009, Annual review of analytical chemistry.

[30]  Rebecca Y Lai,et al.  A folding-based electrochemical aptasensor for detection of vascular endothelial growth factor in human whole blood. , 2011, Biosensors & bioelectronics.

[31]  Ronald Breslow,et al.  Biomimetic Chemistry and Artificial Enzymes: Catalysis by Design , 1995 .

[32]  Xindong Wang,et al.  2D ultrathin nanosheets of Co-Al layered double hydroxides prepared in l-asparagine solution: enhanced peroxidase-like activity and colorimetric detection of glucose. , 2013, Journal of materials chemistry. B.

[33]  Kemin Wang,et al.  Sensitive detection of DNA methyltransferase activity based on rolling circle amplification technology , 2014 .

[34]  M. Stobiecka.  Novel plasmonic field-enhanced nanoassay for trace detection of proteins. , 2014, Biosensors & bioelectronics.

[35]  Itamar Willner,et al.  Optical aptasensors for the analysis of the vascular endothelial growth factor (VEGF). , 2012, Analytical chemistry.

[36]  Baoxin Li,et al.  In situ growth of positively-charged gold nanoparticles on single-walled carbon nanotubes as a highly active peroxidase mimetic and its application in biosensing. , 2013, Biosensors & bioelectronics.

[37]  Guonan Chen,et al.  Highly-efficient peroxidase-like catalytic activity of graphene dots for biosensing. , 2013, Biosensors & bioelectronics.

[38]  Yu Zhang,et al.  Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. , 2007, Nature nanotechnology.

[39]  R. Roskoski,et al.  Vascular endothelial growth factor (VEGF) signaling in tumor progression. , 2007, Critical reviews in oncology/hematology.

[40]  Wei-Yu Chen,et al.  Use of fluorescent DNA-templated gold/silver nanoclusters for the detection of sulfide ions. , 2011, Analytical chemistry.

[41]  A. Mitsuhashi,et al.  Serum vascular endothelial growth factor (VEGF) and VEGF‐C levels as tumor markers in patients with cervical carcinoma , 2005, Cancer.

[42]  Jing Li,et al.  Understanding the formation of CuS concave superstructures with peroxidase-like activity. , 2012, Nanoscale.

[43]  M. Freund,et al.  Potentiometric sensors based on the inductive effect on the pK(a) of poly(aniline): a nonenzymatic glucose sensor. , 2001, Journal of the American Chemical Society.

[44]  M. E. Williams,et al.  Inorganic biomimetic nanostructures. , 2009, Current opinion in chemical biology.

[45]  M. Ferrari,et al.  Direct evidence for catalase and peroxidase activities of ferritin-platinum nanoparticles. , 2011, Biomaterials.

[46]  P. Carmeliet,et al.  Angiogenesis in cancer and other diseases , 2000, Nature.

[47]  L. Gold,et al.  Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. , 1990, Science.

[48]  Yasar Gurbuz,et al.  Capacitive aptamer–antibody based sandwich assay for the detection of VEGF cancer biomarker in serum , 2015 .

[49]  Yu-Ting Su,et al.  Detection of copper ions through recovery of the fluorescence of DNA-templated copper/silver nanoclusters in the presence of mercaptopropionic acid. , 2010, Analytical chemistry.

[50]  Xiaohong Wang,et al.  Fabrication of an inorganic–organic hybrid based on an iron-substituted polyoxotungstate as a peroxidase for colorimetric immunoassays of H2O2 and cancer cells , 2013 .

[51]  K. Hagihara,et al.  Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial growth factor production in rheumatoid arthritis. , 2003, Arthritis and rheumatism.

[52]  Min Zhao,et al.  Intrinsic peroxidase-like activity and catalase-like activity of Co3O4 nanoparticles. , 2012, Chemical communications.

[53]  C. Pederzolli,et al.  An easy way to realize SPR aptasensor: A multimode plastic optical fiber platform for cancer biomarkers detection. , 2015, Talanta.