Nanostructured Silicon Enabled HR-MS for the Label-Free Detection of Biomarkers in Colorectal Cancer Plasma Small Extracellular Vesicles
Despite improvements in treatment options for advanced colorectal cancer (CRC), survival outcomes are still best for patients with non-metastasised disease. Diagnostic tools to identify blood-based biomarkers and assist in CRC subtype classification could afford a means to track CRC progression and...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Journal of Nanotheranostics |
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| Online Access: | https://www.mdpi.com/2624-845X/3/4/13 |
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| author | Sanduru Thamarai Krishnan David Rudd Rana Rahmani E. Eduardo Antunez Rajpreet Singh Minhas Chandra Kirana Guy J. Maddern Kevin Fenix Ehud Hauben Nicolas H. Voelcker |
| author_facet | Sanduru Thamarai Krishnan David Rudd Rana Rahmani E. Eduardo Antunez Rajpreet Singh Minhas Chandra Kirana Guy J. Maddern Kevin Fenix Ehud Hauben Nicolas H. Voelcker |
| author_sort | Sanduru Thamarai Krishnan |
| collection | DOAJ |
| description | Despite improvements in treatment options for advanced colorectal cancer (CRC), survival outcomes are still best for patients with non-metastasised disease. Diagnostic tools to identify blood-based biomarkers and assist in CRC subtype classification could afford a means to track CRC progression and treatment response. Cancer cell-derived small extracellular vesicles (EVs) circulating in blood carry an elevated cargo of lipids and proteins that could be used as a signature of tumour suppressor/promoting events or stages leading up to and including metastasis. Here, we used pre-characterised biobanked plasma samples from surgical units, typically with a low volume (~100 µL), to generate and discover signatures of CRC-derived EVs. We employed nanostructured porous silicon (pSi) surface assisted-laser desorption/ionisation (SALDI) coupled with high-resolution mass spectrometry (HR-MS), to allow sensitive detection of low abundant analytes in plasma EVs. When applied to CRC samples, SALDI-HR-MS enabled the detection of the peptide mass fingerprint of cancer suppressor proteins, including serine/threonine phosphatases and activating-transcription factor 3. SALDI-HR-MS also allowed the detection of a spectrum of glycerophospholipids and sphingolipid signatures in metastatic CRC. We observed that lithium chloride enhanced detection sensitivity to elucidate the structure of low abundant lipids in plasma EVs. pSi SALDI can be used as an effective system for label-free and high throughput analysis of low-volume patient samples, allowing rapid and sensitive analysis for CRC classification. |
| first_indexed | 2024-03-09T16:13:46Z |
| format | Article |
| id | doaj.art-483a18a5973549e6a9eb3cfc3659e07c |
| institution | Directory Open Access Journal |
| issn | 2624-845X |
| language | English |
| last_indexed | 2024-03-09T16:13:46Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Nanotheranostics |
| spelling | doaj.art-483a18a5973549e6a9eb3cfc3659e07c2023-11-24T15:58:58ZengMDPI AGJournal of Nanotheranostics2624-845X2022-10-013418920210.3390/jnt3040013Nanostructured Silicon Enabled HR-MS for the Label-Free Detection of Biomarkers in Colorectal Cancer Plasma Small Extracellular VesiclesSanduru Thamarai Krishnan0David Rudd1Rana Rahmani2E. Eduardo Antunez3Rajpreet Singh Minhas4Chandra Kirana5Guy J. Maddern6Kevin Fenix7Ehud Hauben8Nicolas H. Voelcker9Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, AustraliaDrug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, AustraliaDrug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, AustraliaDrug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, AustraliaDrug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, AustraliaThe Basil Hetzel Institute for Translational Health Research, Woodville 5011, AustraliaThe Basil Hetzel Institute for Translational Health Research, Woodville 5011, AustraliaThe Basil Hetzel Institute for Translational Health Research, Woodville 5011, AustraliaThe Basil Hetzel Institute for Translational Health Research, Woodville 5011, AustraliaDrug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, AustraliaDespite improvements in treatment options for advanced colorectal cancer (CRC), survival outcomes are still best for patients with non-metastasised disease. Diagnostic tools to identify blood-based biomarkers and assist in CRC subtype classification could afford a means to track CRC progression and treatment response. Cancer cell-derived small extracellular vesicles (EVs) circulating in blood carry an elevated cargo of lipids and proteins that could be used as a signature of tumour suppressor/promoting events or stages leading up to and including metastasis. Here, we used pre-characterised biobanked plasma samples from surgical units, typically with a low volume (~100 µL), to generate and discover signatures of CRC-derived EVs. We employed nanostructured porous silicon (pSi) surface assisted-laser desorption/ionisation (SALDI) coupled with high-resolution mass spectrometry (HR-MS), to allow sensitive detection of low abundant analytes in plasma EVs. When applied to CRC samples, SALDI-HR-MS enabled the detection of the peptide mass fingerprint of cancer suppressor proteins, including serine/threonine phosphatases and activating-transcription factor 3. SALDI-HR-MS also allowed the detection of a spectrum of glycerophospholipids and sphingolipid signatures in metastatic CRC. We observed that lithium chloride enhanced detection sensitivity to elucidate the structure of low abundant lipids in plasma EVs. pSi SALDI can be used as an effective system for label-free and high throughput analysis of low-volume patient samples, allowing rapid and sensitive analysis for CRC classification.https://www.mdpi.com/2624-845X/3/4/13high-resolution mass spectrometersmall extracellular vesiclesexosome detectioncolorectal cancer diagnosislabel-free omics and surface assisted-laser desorption/ionisation |
| spellingShingle | Sanduru Thamarai Krishnan David Rudd Rana Rahmani E. Eduardo Antunez Rajpreet Singh Minhas Chandra Kirana Guy J. Maddern Kevin Fenix Ehud Hauben Nicolas H. Voelcker Nanostructured Silicon Enabled HR-MS for the Label-Free Detection of Biomarkers in Colorectal Cancer Plasma Small Extracellular Vesicles Journal of Nanotheranostics high-resolution mass spectrometer small extracellular vesicles exosome detection colorectal cancer diagnosis label-free omics and surface assisted-laser desorption/ionisation |
| title | Nanostructured Silicon Enabled HR-MS for the Label-Free Detection of Biomarkers in Colorectal Cancer Plasma Small Extracellular Vesicles |
| title_full | Nanostructured Silicon Enabled HR-MS for the Label-Free Detection of Biomarkers in Colorectal Cancer Plasma Small Extracellular Vesicles |
| title_fullStr | Nanostructured Silicon Enabled HR-MS for the Label-Free Detection of Biomarkers in Colorectal Cancer Plasma Small Extracellular Vesicles |
| title_full_unstemmed | Nanostructured Silicon Enabled HR-MS for the Label-Free Detection of Biomarkers in Colorectal Cancer Plasma Small Extracellular Vesicles |
| title_short | Nanostructured Silicon Enabled HR-MS for the Label-Free Detection of Biomarkers in Colorectal Cancer Plasma Small Extracellular Vesicles |
| title_sort | nanostructured silicon enabled hr ms for the label free detection of biomarkers in colorectal cancer plasma small extracellular vesicles |
| topic | high-resolution mass spectrometer small extracellular vesicles exosome detection colorectal cancer diagnosis label-free omics and surface assisted-laser desorption/ionisation |
| url | https://www.mdpi.com/2624-845X/3/4/13 |
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