Related Experiment Video
Updated: Oct 29, 2025
Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers
Published on: July 17, 2012
A non-toxic, reversibly released imaging probe for oral cancer that is derived from natural compounds
Magda Ghanim1, Nicola Relitti2, Gavin McManus1
1School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
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.
Insights
A novel fluorescent probe, HA-FA-HEG-OE, targets CD44 receptors, aiding oral cancer detection. This non-toxic imaging agent shows reversible uptake, promising for real-time intraoperative guidance.
Area of Science:
- Biomedical Imaging
- Molecular Oncology
- Nanotechnology
Background:
- CD44 receptor is a key biomarker in various cancers, including oral cancer.
- Surgical resection for oral cancer often leads to significant morbidity.
- Optical imaging agents can improve tumor identification during surgery.
Purpose of the Study:
- To synthesize and characterize a novel, water-soluble fluorescent probe for oral cancer imaging.
- To investigate the probe's uptake mechanism and its relationship with tumorigenic potential.
- To evaluate the probe's suitability for real-time intraoperative imaging.
Main Methods:
- Synthesis of HA-FA-HEG-OE (compound 1) from natural sources (oleic acid, ferulic acid, hyaluronic acid).
- In vitro assessment of compound 1's cytotoxicity, aggregation-induced emission, and intracellular accumulation in SCC-9 oral squamous cells.
- Investigation of compound 1's internalization pathway via CD44 receptor-mediated endocytosis.
- Comparative uptake studies in oral cancer cells with varying tumorigenic potential (SCC-9, DOK, MCF-7).
Main Results:
- Compound 1 is non-toxic, exhibits aggregation-induced emission, and accumulates in vesicles within SCC-9 cells.
- Cellular uptake of compound 1 is reversible and mediated by the CD44 receptor through endocytosis.
- Uptake correlates with tumorigenic potential; lower levels observed in non-tumorigenic and poorly tumorigenic cells.
- The probe's mechanism highlights the role of endocytosis in cancer progression.
Conclusions:
- HA-FA-HEG-OE is a promising, non-toxic fluorescent probe for oral cancer detection.
- CD44 receptor-mediated endocytosis is crucial for probe uptake and correlates with cancer potential.
- The probe's reversible nature and specific targeting make it suitable for real-time intraoperative imaging in oral cancer surgery.
