Gold-loaded nanoporous iron oxide nanocubes: a novel dispersible capture agent for tumor-associated autoantibody analysis in serum.

Autoantibodies are produced against tumor associated antigens (TAAs) long before the appearance of any symptoms and thus can serve as promising, non-invasive biomarkers for early diagnosis of cancer. Current conventional methods for autoantibody detection are highly invasive and mostly provide diagnosis in the later stages of cancer. Herein we report a new electrochemical method for early detection of p53 autoantibodies against colon cancer using a strategy that combines the strength of gold-loaded nanoporous iron oxide nanocube (Au@NPFe2O3NC)-based capture and purification while incorporating the inherent simplicity, inexpensive, and portable nature of the electrochemical and naked-eye colorimetric readouts. After the functionalisation of Au@NPFe2O3NC with p53 antigens, our method utilises a two-step strategy that involves (i) magnetic capture and isolation of autoantibodies using p53/Au@NPFe2O3NC as 'dispersible nanocapture agents' in serum samples and (ii) subsequent detection of autoantibodies through a peroxidase-catalyzed reaction on a commercially available disposable screen-printed electrode or naked-eye detection in an Eppendorf tube. This method has demonstrated a good sensitivity (LOD = 0.02 U mL-1) and reproducibility (relative standard deviation, %RSD = <5%, for n = 3) for detecting p53 autoantibodies in serum and has also been successfully applied to analyse a small cohort of clinical samples obtained from colorectal cancer. We believe that the highly inexpensive, rapid, sensitive, and specific nature of our assay could potentially aid in the development of an early diagnostic tool for cancer and related diseases.

[1]  D. Messadi,et al.  Diagnostic aids for detection of oral precancerous conditions , 2013, International Journal of Oral Science.

[2]  Y. Ho,et al.  Irinotecan and colorectal cancer: the role of p53, VEGF-C and α-B-crystallin expression , 2010, International Journal of Colorectal Disease.

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

[4]  T. Soussi,et al.  p53 Antibodies in the sera of patients with various types of cancer: a review. , 2000, Cancer research.

[5]  S. Dou,et al.  Novel synthesis of superparamagnetic Ni-Co-B nanoparticles and their effect on superconductor properties of MgB2 , 2014 .

[6]  David E. Misek,et al.  Development of natural protein microarrays for diagnosing cancer based on an antibody response to tumor antigens. , 2004, Journal of proteome research.

[7]  M. A. Syed Advances in nanodiagnostic techniques for microbial agents. , 2014, Biosensors & bioelectronics.

[8]  J. Wong,et al.  Esophageal small cell carcinomas: clinicopathologic parameters, p53 overexpression, proliferation marker, and their impact on pathogenesis. , 2000, Archives of pathology & laboratory medicine.

[9]  Hugh Barr,et al.  Raman spectroscopy, a potential tool for the objective identification and classification of neoplasia in Barrett's oesophagus , 2003, The Journal of pathology.

[10]  Kim-Anh Do,et al.  Fingerprinting the circulating repertoire of antibodies from cancer patients , 2003, Nature Biotechnology.

[11]  Ruth Etzioni,et al.  Early detection: The case for early detection , 2003, Nature Reviews Cancer.

[12]  Y. Yamauchi,et al.  Rational design of mesoporous metals and related nanomaterials by a soft-template approach. , 2008, Chemistry, an Asian journal.

[13]  M. Chatterjee,et al.  Usage of cancer associated autoantibodies in the detection of disease. , 2010, Cancer biomarkers : section A of Disease markers.

[14]  M. Rubin,et al.  Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients , 2016, PloS one.

[15]  Colleen E Krause,et al.  Electrochemistry-based approaches to low cost, high sensitivity, automated, multiplexed protein immunoassays for cancer diagnostics. , 2016, The Analyst.

[16]  S. Metcalfe,et al.  P53 autoantibodies in 1006 patients followed up for breast cancer , 2000, Breast Cancer Research.

[17]  M Ferdeghini,et al.  Assessment of the prognostic relevance of serum anti-p53 antibodies in epithelial ovarian cancer. , 1999, Gynecologic oncology.

[18]  Hwee Tong Tan,et al.  Serum autoantibodies as biomarkers for early cancer detection , 2009, The FEBS journal.

[19]  Y. Bahk,et al.  Tumor-associated autoantibodies as diagnostic and prognostic biomarkers , 2012, BMB reports.

[20]  U Menon,et al.  Early detection of cancer in the general population: a blinded case–control study of p53 autoantibodies in colorectal cancer , 2012, British Journal of Cancer.

[21]  D M Eddy,et al.  Secondary prevention of cancer: an overview. , 1986, Bulletin of the World Health Organization.

[22]  E. Petricoin,et al.  Early detection: Proteomic applications for the early detection of cancer , 2003, Nature Reviews Cancer.

[23]  M. Hollingsworth,et al.  Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes. , 2010, Cancer research.

[24]  E. Diamandis,et al.  High throughput proteomic strategies for identifying tumour-associated antigens. , 2007, Cancer letters.

[25]  M. Morales,et al.  The internal structure of magnetic nanoparticles determines the magnetic response. , 2017, Nanoscale.

[26]  A. Walcarius,et al.  Mesoporous Materials‐Based Electrochemical Enzymatic Biosensors , 2015 .

[27]  M. Caron,et al.  Usefulness of autoantigens depletion to detect autoantibody signatures by multiple affinity protein profiling. , 2007, Journal of separation science.

[28]  Y. Yamauchi,et al.  Synthesis of Superparamagnetic Nanoporous Iron Oxide Particles with Hollow Interiors by Using Prussian Blue Coordination Polymers , 2012 .

[29]  N. Morgan,et al.  Electrochemical immunosensors for detection of cancer protein biomarkers. , 2012, ACS nano.

[30]  A. Miller,et al.  The importance of early symptom recognition in the context of early detection and cancer survival. , 2009, European journal of cancer.

[31]  L. Carrascosa,et al.  Electrochemical detection of protein glycosylation using lectin and protein-gold affinity interactions. , 2016, The Analyst.

[32]  Victor Malgras,et al.  Prussian Blue Derived Nanoporous Iron Oxides as Anticancer Drug Carriers for Magnetic-Guided Chemotherapy. , 2015, Chemistry, an Asian journal.

[33]  S. Campuzano,et al.  Toward Liquid Biopsy: Determination of the Humoral Immune Response in Cancer Patients Using HaloTag Fusion Protein-Modified Electrochemical Bioplatforms. , 2016, Analytical chemistry.

[34]  Jack F Douglas,et al.  Interaction of gold nanoparticles with common human blood proteins. , 2010, ACS nano.

[35]  B. Milleron,et al.  Monitoring of p53 autoantibodies in lung cancer during therapy: relationship to response to treatment. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[36]  Simon Law,et al.  The clinicopathological significance of p21 and p53 expression in esophageal squamous cell carcinoma: an analysis of 153 patients , 1999, American Journal of Gastroenterology.

[37]  Richard C. Willson,et al.  Tuning the Magnetic Properties of Nanoparticles , 2013, International journal of molecular sciences.

[38]  P. Solanki,et al.  Nanostructured metal oxide-based biosensors , 2011 .

[39]  K. Hemminki,et al.  p53 autoantibodies predict subsequent development of cancer , 2005, International journal of cancer.

[40]  M. Ziman,et al.  Serologic Autoantibodies as Diagnostic Cancer Biomarkers—A Review , 2013, Cancer Epidemiology, Biomarkers & Prevention.

[41]  Abu Ali Ibn Sina,et al.  Detection of aberrant protein phosphorylation in cancer using direct gold-protein affinity interactions. , 2017, Biosensors & bioelectronics.

[42]  Lee Josephson,et al.  Magnetic Nanoparticle Sensors , 2009, Sensors.

[43]  J. Solassol,et al.  Autoantibody signatures: progress and perspectives for early cancer detection , 2011, Journal of cellular and molecular medicine.

[44]  H. Car,et al.  Magnetic nanoparticles as new diagnostic tools in medicine. , 2012, Advances in medical sciences.

[45]  D. Fiorani,et al.  Size dependence of the spin-flop transition in hematite nanoparticles , 2003 .

[46]  S. Leinster,et al.  The relationship between serum p53 autoantibodies and characteristics of human breast cancer. , 1994, British Journal of Cancer.

[47]  Cuiling Li,et al.  Nanoarchitectures for Mesoporous Metals , 2016, Advanced materials.

[48]  D. Shi,et al.  Synthesis-Dependent Surface Defects and Morphology of Hematite Nanoparticles and Their Effect on Cytotoxicity in Vitro. , 2016, ACS applied materials & interfaces.