A non-toxic, reversibly released imaging probe for oral cancer that is derived from natural compounds
Abstract CD44 is emerging as an important receptor biomarker for various cancers. Amongst these is oral cancer, where surgical resection remains an essential mode of treatment. Unfortunately, surgery is frequently associated with permanent disfigurement, malnutrition, and functional comorbidities du...
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Nature Portfolio
2021
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oai:doaj.org-article:9ef5f59b2e7b4659947e0657bc72efe22021-12-02T16:14:47ZA non-toxic, reversibly released imaging probe for oral cancer that is derived from natural compounds10.1038/s41598-021-93408-02045-2322https://doaj.org/article/9ef5f59b2e7b4659947e0657bc72efe22021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93408-0https://doaj.org/toc/2045-2322Abstract CD44 is emerging as an important receptor biomarker for various cancers. Amongst these is oral cancer, where surgical resection remains an essential mode of treatment. Unfortunately, surgery is frequently associated with permanent disfigurement, malnutrition, and functional comorbidities due to the difficultly of tumour removal. Optical imaging agents that can guide tumour tissue identification represent an attractive approach to minimising the impact of surgery. Here, we report the synthesis of a water-soluble fluorescent probe, namely HA-FA-HEG-OE (compound 1), that comprises components originating from natural sources: oleic acid, ferulic acid and hyaluronic acid. Compound 1 was found to be non-toxic, displayed aggregation induced emission and accumulated intracellularly in vesicles in SCC-9 oral squamous cells. The uptake of 1 was fully reversible over time. Internalization of compound 1 occurs through receptor mediated endocytosis; uniquely mediated through the CD44 receptor. Uptake is related to tumorigenic potential, with non-tumorigenic, dysplastic DOK cells and poorly tumorigenic MCF-7 cells showing only low intracellular levels and highlighting the critical role of endocytosis in cancer progression and metastasis. Together, the recognised importance of CD44 as a cancer stem cell marker in oral cancer, and the reversible, non-toxic nature of 1, makes it a promising agent for real time intraoperative imaging.Magda GhanimNicola RelittiGavin McManusStefania ButiniAndrea CappelliGiuseppe CampianiK. H. MokVincent P. KellyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
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Medicine R Science Q Magda Ghanim Nicola Relitti Gavin McManus Stefania Butini Andrea Cappelli Giuseppe Campiani K. H. Mok Vincent P. Kelly A non-toxic, reversibly released imaging probe for oral cancer that is derived from natural compounds |
description |
Abstract CD44 is emerging as an important receptor biomarker for various cancers. Amongst these is oral cancer, where surgical resection remains an essential mode of treatment. Unfortunately, surgery is frequently associated with permanent disfigurement, malnutrition, and functional comorbidities due to the difficultly of tumour removal. Optical imaging agents that can guide tumour tissue identification represent an attractive approach to minimising the impact of surgery. Here, we report the synthesis of a water-soluble fluorescent probe, namely HA-FA-HEG-OE (compound 1), that comprises components originating from natural sources: oleic acid, ferulic acid and hyaluronic acid. Compound 1 was found to be non-toxic, displayed aggregation induced emission and accumulated intracellularly in vesicles in SCC-9 oral squamous cells. The uptake of 1 was fully reversible over time. Internalization of compound 1 occurs through receptor mediated endocytosis; uniquely mediated through the CD44 receptor. Uptake is related to tumorigenic potential, with non-tumorigenic, dysplastic DOK cells and poorly tumorigenic MCF-7 cells showing only low intracellular levels and highlighting the critical role of endocytosis in cancer progression and metastasis. Together, the recognised importance of CD44 as a cancer stem cell marker in oral cancer, and the reversible, non-toxic nature of 1, makes it a promising agent for real time intraoperative imaging. |
format |
article |
author |
Magda Ghanim Nicola Relitti Gavin McManus Stefania Butini Andrea Cappelli Giuseppe Campiani K. H. Mok Vincent P. Kelly |
author_facet |
Magda Ghanim Nicola Relitti Gavin McManus Stefania Butini Andrea Cappelli Giuseppe Campiani K. H. Mok Vincent P. Kelly |
author_sort |
Magda Ghanim |
title |
A non-toxic, reversibly released imaging probe for oral cancer that is derived from natural compounds |
title_short |
A non-toxic, reversibly released imaging probe for oral cancer that is derived from natural compounds |
title_full |
A non-toxic, reversibly released imaging probe for oral cancer that is derived from natural compounds |
title_fullStr |
A non-toxic, reversibly released imaging probe for oral cancer that is derived from natural compounds |
title_full_unstemmed |
A non-toxic, reversibly released imaging probe for oral cancer that is derived from natural compounds |
title_sort |
non-toxic, reversibly released imaging probe for oral cancer that is derived from natural compounds |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/9ef5f59b2e7b4659947e0657bc72efe2 |
work_keys_str_mv |
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