Quantification of Circulating Cancer Biomarkers via Sensitive Topographic Measurements on Single Binder Nanoarrays

ACS Omega
Elena AmbrosettiLoredana Casalis

Abstract

Early detection of cancer plays a crucial role in disease prognosis. It requires the recognition and quantification of low amounts of specific molecular biomarkers, either free or transported inside nanovesicles, through the development of novel sensitive diagnostic technologies. In this context, we have developed a nanoarray platform for the noninvasive quantification of cancer biomarkers circulating in the bloodstream. The assay is based on molecular manipulation to create functional spots of surface-immobilized binders and differential topography measurements. It is label-free and requires just a single binder per antigen, and when it is implemented with fluorescence labeling/readout, it can be used for epitope mapping. As a benchmark, we focused on the plasma release of Her2 extracellular domain (ECD), a proposed biomarker for the progression of Her2-positive tumors and response to anticancer therapies. By employing robust, easily engineered camelid nanobodies as binders, we measured ECD-Her2 concentrations in the range of the actual clinical cutoff value for Her2-positive breast cancer. The specificity for Her2 detection was preserved when it was measured in parallel with other potential biomarkers, demonstrating a forthco...Continue Reading

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Citations

Oct 20, 2017·Veterinary and Comparative Oncology·E Mazzega, A de Marco
Nov 7, 2019·Chemical Communications : Chem Comm·Miguel A SolerSara Fortuna
Apr 17, 2019·Applied Microbiology and Biotechnology·Sandra OloketuyiArio de Marco
Apr 15, 2020·Protein Expression and Purification·Ario de Marco
Apr 20, 2021·Applied Biochemistry and Biotechnology·Oginni Gbenga FolorunshoArio de Marco
May 25, 2021·ACS Nano·Arif E CetinAli Khademhosseini

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Methods Mentioned

BETA
surface plasmon resonance
atomic force microscopy
AFM
biosensor
enzyme-linked immunosorbent assays
ELISA
fluorescence microscopy
immunoprecipitation
biopsy
footprinting

Software Mentioned

BIAevaluation

Related Concepts

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