Imaging of Light-Enhanced Extracellular Vesicle-Mediated Delivery of Oxaliplatin to Colorectal Cancer Cells via Laser Ablation, Inductively Coupled Plasma Mass Spectrometry
Extracellular vesicles (EVs) are lipid bilayer structures released by all cells that mediate cell-to-cell communication via the transfer of bioactive cargo. Because of the natural origin of EVs, their efficient uptake by recipient cells, capacity to stabilize and transport biomolecules and their pot...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/13/1/24 |
| _version_ | 1797358976836304896 |
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| author | Kara Chandler Josh Millar George Ward Christopher Boyall Tom White Joseph David Ready Rawan Maani Keith Chapple Robert Tempest Joseph Brealey Catherine Duckett Sarah Haywood-Small Simon Turega Nick Peake |
| author_facet | Kara Chandler Josh Millar George Ward Christopher Boyall Tom White Joseph David Ready Rawan Maani Keith Chapple Robert Tempest Joseph Brealey Catherine Duckett Sarah Haywood-Small Simon Turega Nick Peake |
| author_sort | Kara Chandler |
| collection | DOAJ |
| description | Extracellular vesicles (EVs) are lipid bilayer structures released by all cells that mediate cell-to-cell communication via the transfer of bioactive cargo. Because of the natural origin of EVs, their efficient uptake by recipient cells, capacity to stabilize and transport biomolecules and their potential for cell/tissue targeting and preferential uptake by cancer cells, they have enormous potential for bioengineering into improved and targeted drug delivery systems. In this work, we investigated the use of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) as a tool to measure the loading of platinum-based chemotherapeutic agents. The EV loading of oxaliplatin via co-incubation was demonstrated, and LA-ICP-MS imaging showed greater efficiency of delivery to colorectal cancer cells compared to free oxaliplatin, leading to enhanced cytotoxic effect. Further, the impact of EV co-loading with a porphyrin (C5SHU, known as ‘C5’) photosensitizer on oxaliplatin delivery was assessed. Fluorescence analysis using nano-flow cytometry showed dose-dependent EV loading as well as a trend towards the loading of larger particles. Exposure of OXA-C5-EV-treated colorectal cancer cells to light indicated that delivery was enhanced by both light exposure and porphyrins, with a synergistic effect on cell viability observed between oxaliplatin, EVs and light exposure after the delivery of the co-loaded EVs. In summary, this work demonstrates the utility of LA-ICP-MS and mass spectrometry imaging in assessing the loading efficiency and cellular delivery of platinum-based therapeutics, which would also be suitable for agents containing other elements, confirms that EVs are more efficient at delivery compared to free drugs, and describes the use of light exposure in optimizing delivery and therapeutic effects of EV-mediated drug delivery both in combination and independently of porphyrin-based photosensitizers. |
| first_indexed | 2024-03-08T15:09:59Z |
| format | Article |
| id | doaj.art-01b7d8de889a4170848fe6f1a65090dd |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-08T15:09:59Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-01b7d8de889a4170848fe6f1a65090dd2024-01-10T14:53:13ZengMDPI AGCells2073-44092023-12-011312410.3390/cells13010024Imaging of Light-Enhanced Extracellular Vesicle-Mediated Delivery of Oxaliplatin to Colorectal Cancer Cells via Laser Ablation, Inductively Coupled Plasma Mass SpectrometryKara Chandler0Josh Millar1George Ward2Christopher Boyall3Tom White4Joseph David Ready5Rawan Maani6Keith Chapple7Robert Tempest8Joseph Brealey9Catherine Duckett10Sarah Haywood-Small11Simon Turega12Nick Peake13Biomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UKBiomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UKBiomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UKBiomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UKBiomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UKBiomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UKBiomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UKDepartment of General Surgery, Sheffield Teaching Hospitals, NHS Foundation Trust, Sheffield S5 7AU, UKBiomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UKNanoFCM Co., Ltd., Medicity, D6 Thane Road, Nottingham NG60 6BH, UKBiomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UKBiomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UKBiomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UKBiomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UKExtracellular vesicles (EVs) are lipid bilayer structures released by all cells that mediate cell-to-cell communication via the transfer of bioactive cargo. Because of the natural origin of EVs, their efficient uptake by recipient cells, capacity to stabilize and transport biomolecules and their potential for cell/tissue targeting and preferential uptake by cancer cells, they have enormous potential for bioengineering into improved and targeted drug delivery systems. In this work, we investigated the use of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) as a tool to measure the loading of platinum-based chemotherapeutic agents. The EV loading of oxaliplatin via co-incubation was demonstrated, and LA-ICP-MS imaging showed greater efficiency of delivery to colorectal cancer cells compared to free oxaliplatin, leading to enhanced cytotoxic effect. Further, the impact of EV co-loading with a porphyrin (C5SHU, known as ‘C5’) photosensitizer on oxaliplatin delivery was assessed. Fluorescence analysis using nano-flow cytometry showed dose-dependent EV loading as well as a trend towards the loading of larger particles. Exposure of OXA-C5-EV-treated colorectal cancer cells to light indicated that delivery was enhanced by both light exposure and porphyrins, with a synergistic effect on cell viability observed between oxaliplatin, EVs and light exposure after the delivery of the co-loaded EVs. In summary, this work demonstrates the utility of LA-ICP-MS and mass spectrometry imaging in assessing the loading efficiency and cellular delivery of platinum-based therapeutics, which would also be suitable for agents containing other elements, confirms that EVs are more efficient at delivery compared to free drugs, and describes the use of light exposure in optimizing delivery and therapeutic effects of EV-mediated drug delivery both in combination and independently of porphyrin-based photosensitizers.https://www.mdpi.com/2073-4409/13/1/24laser-ablation inductively coupled plasma mass spectrometryextracellular vesicleoxaliplatinphotosensitizerscolorectal cancer |
| spellingShingle | Kara Chandler Josh Millar George Ward Christopher Boyall Tom White Joseph David Ready Rawan Maani Keith Chapple Robert Tempest Joseph Brealey Catherine Duckett Sarah Haywood-Small Simon Turega Nick Peake Imaging of Light-Enhanced Extracellular Vesicle-Mediated Delivery of Oxaliplatin to Colorectal Cancer Cells via Laser Ablation, Inductively Coupled Plasma Mass Spectrometry Cells laser-ablation inductively coupled plasma mass spectrometry extracellular vesicle oxaliplatin photosensitizers colorectal cancer |
| title | Imaging of Light-Enhanced Extracellular Vesicle-Mediated Delivery of Oxaliplatin to Colorectal Cancer Cells via Laser Ablation, Inductively Coupled Plasma Mass Spectrometry |
| title_full | Imaging of Light-Enhanced Extracellular Vesicle-Mediated Delivery of Oxaliplatin to Colorectal Cancer Cells via Laser Ablation, Inductively Coupled Plasma Mass Spectrometry |
| title_fullStr | Imaging of Light-Enhanced Extracellular Vesicle-Mediated Delivery of Oxaliplatin to Colorectal Cancer Cells via Laser Ablation, Inductively Coupled Plasma Mass Spectrometry |
| title_full_unstemmed | Imaging of Light-Enhanced Extracellular Vesicle-Mediated Delivery of Oxaliplatin to Colorectal Cancer Cells via Laser Ablation, Inductively Coupled Plasma Mass Spectrometry |
| title_short | Imaging of Light-Enhanced Extracellular Vesicle-Mediated Delivery of Oxaliplatin to Colorectal Cancer Cells via Laser Ablation, Inductively Coupled Plasma Mass Spectrometry |
| title_sort | imaging of light enhanced extracellular vesicle mediated delivery of oxaliplatin to colorectal cancer cells via laser ablation inductively coupled plasma mass spectrometry |
| topic | laser-ablation inductively coupled plasma mass spectrometry extracellular vesicle oxaliplatin photosensitizers colorectal cancer |
| url | https://www.mdpi.com/2073-4409/13/1/24 |
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