TY - JOUR
T1 - Converting the personalized biomolecular corona of graphene oxide nanoflakes into a high-throughput diagnostic test for early cancer detection
AU - Papi, Massimiliano
AU - Palmieri, Valentina
AU - Digiacomo, Luca
AU - Giulimondi, Francesca
AU - Palchetti, Sara
AU - Ciasca, Gabriele
AU - Perini, Giordano
AU - Caputo, Damiano
AU - Cartillone, Maria Cristina
AU - Cascone, Chiara
AU - Coppola, Roberto
AU - Capriotti, Anna Laura
AU - Laganà, Aldo
AU - Pozzi, Daniela
AU - Caracciolo, Giulio
PY - 2019/8/15
Y1 - 2019/8/15
N2 - Advances in nanotechnology are introducing the exciting possibility of cancer identification at early stages via analysis of the personalized biomolecular corona (BC), i.e. the dynamic "halo" of proteins that adsorbs onto NPs following exposure to patients' plasma. In this study, we develop a blood test for early cancer detection based on the characterization of the BC that forms around Graphene Oxide (GO) nanoflakes. Among its elective properties, GO binds low amounts of albumin, the most abundant protein in the blood and one of the most enriched proteins in the BC of many nanomaterials. This unique property of GO allows strong adsorption of poorly concentrated plasma proteins without abundant protein depletion. In our study, GO nanometric flakes have been used to analyze BCs from 50 subjects, half of them diagnosed with pancreatic cancer and half of them being healthy volunteers. Pancreatic cancer was chosen as the model of a high mortality disease with poor survival rates due to its delayed diagnosis. The receiver operating characteristic (ROC) curve analysis was applied to measure the diagnostic accuracy of the BC-based test. We obtained an area under the curve (AUC) of 0.96 and the test discriminated cancer patients from healthy subjects with a sensitivity of 92%. Finally, a double-blind validation was made using a second test dataset (10 healthy subjects + 10 pancreatic cancer patients) and it confirmed the results obtained on the first training dataset. Being highly accurate, fast, inexpensive and easy to perform, we believe that the BC-enabled blood test has the potential to become a turning point in early detection of cancer and other diseases.
AB - Advances in nanotechnology are introducing the exciting possibility of cancer identification at early stages via analysis of the personalized biomolecular corona (BC), i.e. the dynamic "halo" of proteins that adsorbs onto NPs following exposure to patients' plasma. In this study, we develop a blood test for early cancer detection based on the characterization of the BC that forms around Graphene Oxide (GO) nanoflakes. Among its elective properties, GO binds low amounts of albumin, the most abundant protein in the blood and one of the most enriched proteins in the BC of many nanomaterials. This unique property of GO allows strong adsorption of poorly concentrated plasma proteins without abundant protein depletion. In our study, GO nanometric flakes have been used to analyze BCs from 50 subjects, half of them diagnosed with pancreatic cancer and half of them being healthy volunteers. Pancreatic cancer was chosen as the model of a high mortality disease with poor survival rates due to its delayed diagnosis. The receiver operating characteristic (ROC) curve analysis was applied to measure the diagnostic accuracy of the BC-based test. We obtained an area under the curve (AUC) of 0.96 and the test discriminated cancer patients from healthy subjects with a sensitivity of 92%. Finally, a double-blind validation was made using a second test dataset (10 healthy subjects + 10 pancreatic cancer patients) and it confirmed the results obtained on the first training dataset. Being highly accurate, fast, inexpensive and easy to perform, we believe that the BC-enabled blood test has the potential to become a turning point in early detection of cancer and other diseases.
KW - Area Under Curve
KW - Biomarkers, Tumor/blood
KW - CA-19-9 Antigen/blood
KW - Case-Control Studies
KW - Double-Blind Method
KW - Early Detection of Cancer/methods
KW - Graphite/chemistry
KW - High-Throughput Screening Assays
KW - Humans
KW - Nanostructures/chemistry
KW - Pancreatic Neoplasms/diagnosis
KW - Protein Corona/analysis
KW - ROC Curve
KW - Sensitivity and Specificity
U2 - 10.1039/c9nr01413f
DO - 10.1039/c9nr01413f
M3 - Article
C2 - 31386742
SN - 2040-3364
VL - 11
SP - 15339
EP - 15346
JO - Nanoscale
JF - Nanoscale
IS - 32
ER -