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 forthcoming implementation of this approach for multiplexing analysis. Prospectively, this nanorarray platform may be customized to allow for the detection of promising new classes of circulating biomarkers, such as exosomes and microvesicles.

Quantification of Circulating Cancer Biomarkers via Sensitive Topographic Measurements on Single Binder Nanoarrays / Ambrosetti, Elena; Paoletti, Pamela; Bosco, Alessandro; Parisse, Pietro; Scaini, Denis; Tagliabue, Elda; De Marco, Ario; Casalis, Loredana. - In: ACS OMEGA. - ISSN 2470-1343. - 2:6(2017), pp. 2618-2629. [10.1021/acsomega.7b00284]

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

Paoletti, Pamela;Scaini, Denis
Conceptualization
;
2017-01-01

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 forthcoming implementation of this approach for multiplexing analysis. Prospectively, this nanorarray platform may be customized to allow for the detection of promising new classes of circulating biomarkers, such as exosomes and microvesicles.
2017
2
6
2618
2629
pubs.acs.org/journal/acsodf
Ambrosetti, Elena; Paoletti, Pamela; Bosco, Alessandro; Parisse, Pietro; Scaini, Denis; Tagliabue, Elda; De Marco, Ario; Casalis, Loredana
File in questo prodotto:
File Dimensione Formato  
2017 – Quantification of Circulating Cancer Biomarkers via Sensitive Topographic Measurements on Single Binder Nanoarrays.pdf

accesso aperto

Descrizione: ACS AuthorChoice
Tipologia: Versione Editoriale (PDF)
Licenza: Non specificato
Dimensione 4.59 MB
Formato Adobe PDF
4.59 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/71356
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 21
  • ???jsp.display-item.citation.isi??? 18
social impact