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Targeting of epidermal growth factor receptor (EGFR)-positive pancreatic cancer cell lines with cetuximab-conjugated near-infrared silver sulphide quantum dots

Labib, PL; Yaghini, E; Hashemkhani, M; Davidson, BR; MacRobert, AJ; Loizidou, M; Acar, HY; (2019) Targeting of epidermal growth factor receptor (EGFR)-positive pancreatic cancer cell lines with cetuximab-conjugated near-infrared silver sulphide quantum dots. In: 17th International Photodynamic Association World Congress. (pp. p. 1107013). SPIE: Cambridge, Massachusetts, United States. Green open access

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Abstract

Introduction: Fluorescence-guided surgery could potentially reduce local recurrence after pancreatic cancer resection. However, the ideal contrast agent for this purpose is not yet determined. The monoclonal antibody cetuximab targets the EGFR receptor, which is overexpressed in 64% of pancreatic cancers. We investigated the efficacy of near-infrared emitting silver sulphide Quantum Dot (QD)-cetuximab nanoconjugates for targeting EGFR-positive pancreatic cancer. Methods: 2-Mercaptopropionic acid-coated QDs were prepared from AgNO3 and Na2S. Pancreatic cancer cell lines PANC-1 and CFPAC-1 were confirmed EGFR-positive using a commercial AlexaFluor488-cetuximab probe. Nonconjugated QD and cetuximab-conjugated QD (QD-cetuximab) toxicity was assessed after 24 and 48 hours using MTT assay. Fluorescence microscopy was performed following a) formaldehyde-fixed immunofluorescence and b) live staining with QD-cetuximab for four hours at concentrations corresponding to 0, 10, 50, 100, 200, 400 and 600µg ml-1 of silver. Results: Untargeted QDs were non-toxic in both cell lines after 48 hours at all investigated concentrations, whereas QDcetuximab was toxic at 100µg ml-1 after 24 hours in PANC-1 and at 10µg ml-1 in CFPAC-1. Fixed immunofluorescence demonstrated EGFR targeting by QD-cetuximab at concentrations of 50µg ml-1 upwards in both cell lines. Live staining demonstrated similar efficacy of EGFR targeting up to 50µg ml-1 , although a reduction of fluorescence at higher concentrations was observed when compared to fixed immunofluorescence. Conclusion: Silver sulphide QD-cetuximab nanoconjugates have the potential to target live EGFR-positive pancreatic cancer cells at doses of up to 50 µg ml-1 . The reduction in QD fluorescence observed at higher concentrations is likely to be secondary to cetuximab toxicity.

Type: Proceedings paper
Title: Targeting of epidermal growth factor receptor (EGFR)-positive pancreatic cancer cell lines with cetuximab-conjugated near-infrared silver sulphide quantum dots
Event: 17th International Photodynamic Association World Congress
Location: Cambridge, Massachusetts, United States
Dates: 28 June 2019 - 04 July 2019
ISBN-13: 9781510628335
Open access status: An open access version is available from UCL Discovery
DOI: 10.1117/12.2525086
Publisher version: https://doi.org/10.1117/12.2525086
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Quantum dots, epidermal growth factor receptor, pancreatic cancer, photodiagnostics, image-guided surgery
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/10079656
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