Anticipating metastasis through electrochemical immunosensing of tumor hypoxia biomarkers
Metastasis is responsible for about 90% of cancer-associated deaths. In the context of solid tumors, the low oxygen concentration in the tumor microenvironment (hypoxia) is one of the key factors contributing to metastasis. Tumor cells adapt to these conditions by overexpressing certain proteins suc...
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| Veröffentlicht in: | Analytical and bioanalytical chemistry 2022, Vol.414 (1), p.399-412 |
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| creator | Muñoz-San Martín, Cristina Gamella, Maria Pedrero, María Montero-Calle, Ana Pérez-Ginés, Víctor Camps, Jordi Arenas, Meritxell Barderas, Rodrigo Pingarrón, José M. Campuzano, Susana |
| description | Metastasis is responsible for about 90% of cancer-associated deaths. In the context of solid tumors, the low oxygen concentration in the tumor microenvironment (hypoxia) is one of the key factors contributing to metastasis. Tumor cells adapt to these conditions by overexpressing certain proteins such as programmed death ligand 1 (PD-L1) and hypoxia-inducible factor 1 alpha (HIF-1α). However, the determination of these tumor hypoxia markers that can be used to follow-up tumor progression and improve the efficiency of therapies has been scarcely addressed using electrochemical biosensors. In this work, we report the first electrochemical bioplatform for the determination of PD-L1 as well as the first one allowing its simultaneous determination with HIF-1α. The target proteins were captured and enzymatically labeled on magnetic microbeads and amperometric detection was undertaken on the surface of screen-printed dual carbon electrodes using the hydrogen peroxide/peroxidase/hydroquinone system. Sandwich immunoassays were implemented for both the HIF-1α and PD-L1 sensors and the analytical characteristics were evaluated providing LOD values of 86 and 279 pg mL
−1
for the amperometric determination of PD-L1 and HIF-1α standards, respectively. The developed electrochemical immunoplatforms are competitive versus the only electrochemical immunosensor reported for the determination of HIF-1α and the “gold standard” ELISA methodology for the single determination of both proteins in terms of assay time, compatibility with the simultaneous determination of both proteins making their use suitable for untrained users at the point of attention. The dual amperometric immunosensor was applied to the simultaneous determination of HIF-1α and PD-L1 in cancer cell lysates. The analyses lasted only 2 h and just 0.5 μg of the sample was required.
Graphical abstract |
| doi_str_mv | 10.1007/s00216-021-03240-8 |
| format | Article |
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−1
for the amperometric determination of PD-L1 and HIF-1α standards, respectively. The developed electrochemical immunoplatforms are competitive versus the only electrochemical immunosensor reported for the determination of HIF-1α and the “gold standard” ELISA methodology for the single determination of both proteins in terms of assay time, compatibility with the simultaneous determination of both proteins making their use suitable for untrained users at the point of attention. The dual amperometric immunosensor was applied to the simultaneous determination of HIF-1α and PD-L1 in cancer cell lysates. The analyses lasted only 2 h and just 0.5 μg of the sample was required.
Graphical abstract</description><identifier>ISSN: 1618-2642</identifier><identifier>EISSN: 1618-2650</identifier><identifier>DOI: 10.1007/s00216-021-03240-8</identifier><identifier>PMID: 33635388</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>ABCs 20th Anniversary ; Analysis ; Analytical Chemistry ; Apoptosis ; Biochemistry ; Biological markers ; Biomarkers ; Biomarkers, Tumor - analysis ; Biosensing Techniques - methods ; Biosensors ; Cancer ; Characterization and Evaluation of Materials ; Chemistry ; Chemistry and Materials Science ; Electrical measurement ; Electrochemical apparatus ; Electrochemistry ; Enzyme-linked immunosorbent assay ; Food Science ; Humans ; Hydrogen peroxide ; Hydroquinone ; Hypoxia ; Hypoxia-inducible factor 1 ; Hypoxia-inducible factor 1a ; Identification and classification ; Immunoassay ; Immunoassays ; Immunosensors ; Laboratory Medicine ; Lysates ; Metastases ; Metastasis ; Methods ; Microspheres ; Monitoring/Environmental Analysis ; Nanoparticles ; PD-L1 protein ; Peroxidase ; Proteins ; Research Paper ; Sensors ; Solid tumors ; Tumor cells ; Tumor Hypoxia ; Tumor microenvironment ; Tumors</subject><ispartof>Analytical and bioanalytical chemistry, 2022, Vol.414 (1), p.399-412</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2021</rights><rights>2021. Springer-Verlag GmbH Germany, part of Springer Nature.</rights><rights>COPYRIGHT 2022 Springer</rights><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-41bcb026c9c1f18b061692219fe22d5c7870ce9d20f48fd41b86d4c682b00cb83</citedby><cites>FETCH-LOGICAL-c442t-41bcb026c9c1f18b061692219fe22d5c7870ce9d20f48fd41b86d4c682b00cb83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00216-021-03240-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00216-021-03240-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33635388$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Muñoz-San Martín, Cristina</creatorcontrib><creatorcontrib>Gamella, Maria</creatorcontrib><creatorcontrib>Pedrero, María</creatorcontrib><creatorcontrib>Montero-Calle, Ana</creatorcontrib><creatorcontrib>Pérez-Ginés, Víctor</creatorcontrib><creatorcontrib>Camps, Jordi</creatorcontrib><creatorcontrib>Arenas, Meritxell</creatorcontrib><creatorcontrib>Barderas, Rodrigo</creatorcontrib><creatorcontrib>Pingarrón, José M.</creatorcontrib><creatorcontrib>Campuzano, Susana</creatorcontrib><title>Anticipating metastasis through electrochemical immunosensing of tumor hypoxia biomarkers</title><title>Analytical and bioanalytical chemistry</title><addtitle>Anal Bioanal Chem</addtitle><addtitle>Anal Bioanal Chem</addtitle><description>Metastasis is responsible for about 90% of cancer-associated deaths. In the context of solid tumors, the low oxygen concentration in the tumor microenvironment (hypoxia) is one of the key factors contributing to metastasis. Tumor cells adapt to these conditions by overexpressing certain proteins such as programmed death ligand 1 (PD-L1) and hypoxia-inducible factor 1 alpha (HIF-1α). However, the determination of these tumor hypoxia markers that can be used to follow-up tumor progression and improve the efficiency of therapies has been scarcely addressed using electrochemical biosensors. In this work, we report the first electrochemical bioplatform for the determination of PD-L1 as well as the first one allowing its simultaneous determination with HIF-1α. The target proteins were captured and enzymatically labeled on magnetic microbeads and amperometric detection was undertaken on the surface of screen-printed dual carbon electrodes using the hydrogen peroxide/peroxidase/hydroquinone system. Sandwich immunoassays were implemented for both the HIF-1α and PD-L1 sensors and the analytical characteristics were evaluated providing LOD values of 86 and 279 pg mL
−1
for the amperometric determination of PD-L1 and HIF-1α standards, respectively. The developed electrochemical immunoplatforms are competitive versus the only electrochemical immunosensor reported for the determination of HIF-1α and the “gold standard” ELISA methodology for the single determination of both proteins in terms of assay time, compatibility with the simultaneous determination of both proteins making their use suitable for untrained users at the point of attention. The dual amperometric immunosensor was applied to the simultaneous determination of HIF-1α and PD-L1 in cancer cell lysates. The analyses lasted only 2 h and just 0.5 μg of the sample was required.
Graphical abstract</description><subject>ABCs 20th Anniversary</subject><subject>Analysis</subject><subject>Analytical Chemistry</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biological markers</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Biosensing Techniques - methods</subject><subject>Biosensors</subject><subject>Cancer</subject><subject>Characterization and Evaluation of Materials</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Electrical measurement</subject><subject>Electrochemical apparatus</subject><subject>Electrochemistry</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Food Science</subject><subject>Humans</subject><subject>Hydrogen peroxide</subject><subject>Hydroquinone</subject><subject>Hypoxia</subject><subject>Hypoxia-inducible factor 1</subject><subject>Hypoxia-inducible factor 1a</subject><subject>Identification and classification</subject><subject>Immunoassay</subject><subject>Immunoassays</subject><subject>Immunosensors</subject><subject>Laboratory Medicine</subject><subject>Lysates</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Methods</subject><subject>Microspheres</subject><subject>Monitoring/Environmental Analysis</subject><subject>Nanoparticles</subject><subject>PD-L1 protein</subject><subject>Peroxidase</subject><subject>Proteins</subject><subject>Research Paper</subject><subject>Sensors</subject><subject>Solid tumors</subject><subject>Tumor cells</subject><subject>Tumor Hypoxia</subject><subject>Tumor 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metastasis through electrochemical immunosensing of tumor hypoxia biomarkers</title><author>Muñoz-San Martín, Cristina ; Gamella, Maria ; Pedrero, María ; Montero-Calle, Ana ; Pérez-Ginés, Víctor ; Camps, Jordi ; Arenas, Meritxell ; Barderas, Rodrigo ; Pingarrón, José M. ; Campuzano, Susana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-41bcb026c9c1f18b061692219fe22d5c7870ce9d20f48fd41b86d4c682b00cb83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>ABCs 20th Anniversary</topic><topic>Analysis</topic><topic>Analytical Chemistry</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biological markers</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Biosensing Techniques - methods</topic><topic>Biosensors</topic><topic>Cancer</topic><topic>Characterization and Evaluation of 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Susana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anticipating metastasis through electrochemical immunosensing of tumor hypoxia biomarkers</atitle><jtitle>Analytical and bioanalytical chemistry</jtitle><stitle>Anal Bioanal Chem</stitle><addtitle>Anal Bioanal Chem</addtitle><date>2022</date><risdate>2022</risdate><volume>414</volume><issue>1</issue><spage>399</spage><epage>412</epage><pages>399-412</pages><issn>1618-2642</issn><eissn>1618-2650</eissn><abstract>Metastasis is responsible for about 90% of cancer-associated deaths. In the context of solid tumors, the low oxygen concentration in the tumor microenvironment (hypoxia) is one of the key factors contributing to metastasis. Tumor cells adapt to these conditions by overexpressing certain proteins such as programmed death ligand 1 (PD-L1) and hypoxia-inducible factor 1 alpha (HIF-1α). However, the determination of these tumor hypoxia markers that can be used to follow-up tumor progression and improve the efficiency of therapies has been scarcely addressed using electrochemical biosensors. In this work, we report the first electrochemical bioplatform for the determination of PD-L1 as well as the first one allowing its simultaneous determination with HIF-1α. The target proteins were captured and enzymatically labeled on magnetic microbeads and amperometric detection was undertaken on the surface of screen-printed dual carbon electrodes using the hydrogen peroxide/peroxidase/hydroquinone system. Sandwich immunoassays were implemented for both the HIF-1α and PD-L1 sensors and the analytical characteristics were evaluated providing LOD values of 86 and 279 pg mL
−1
for the amperometric determination of PD-L1 and HIF-1α standards, respectively. The developed electrochemical immunoplatforms are competitive versus the only electrochemical immunosensor reported for the determination of HIF-1α and the “gold standard” ELISA methodology for the single determination of both proteins in terms of assay time, compatibility with the simultaneous determination of both proteins making their use suitable for untrained users at the point of attention. The dual amperometric immunosensor was applied to the simultaneous determination of HIF-1α and PD-L1 in cancer cell lysates. The analyses lasted only 2 h and just 0.5 μg of the sample was required.
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| subjects | ABCs 20th Anniversary Analysis Analytical Chemistry Apoptosis Biochemistry Biological markers Biomarkers Biomarkers, Tumor - analysis Biosensing Techniques - methods Biosensors Cancer Characterization and Evaluation of Materials Chemistry Chemistry and Materials Science Electrical measurement Electrochemical apparatus Electrochemistry Enzyme-linked immunosorbent assay Food Science Humans Hydrogen peroxide Hydroquinone Hypoxia Hypoxia-inducible factor 1 Hypoxia-inducible factor 1a Identification and classification Immunoassay Immunoassays Immunosensors Laboratory Medicine Lysates Metastases Metastasis Methods Microspheres Monitoring/Environmental Analysis Nanoparticles PD-L1 protein Peroxidase Proteins Research Paper Sensors Solid tumors Tumor cells Tumor Hypoxia Tumor microenvironment Tumors |
| title | Anticipating metastasis through electrochemical immunosensing of tumor hypoxia biomarkers |
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