Duramycin-porphyrin conjugates for targeting of tumour cells using photodynamic therapy

Broughton, Laura J.; Giuntini, Francesca; Savoie, Huguette; Bryden, Francesca; Boyle, Ross W.; Maraveyas, Anthony; Madden, Leigh A.

Abstract

Duramycin, through binding with phosphatidylethanolamine (PE), has been shown to be a selective molecular probe for the targeting and imaging of cancer cells. Photodynamic therapy aims to bring about specific cytotoxic damage to tumours through delivery of a photosensitising agent and light irradiation. Conjugation to biological molecules that specifically target cancer has been shown to increase photosensitiser (PS) selectivity and decrease damage to surrounding normal tissue. The aim of this study was to target tumour cells with a PE-specific PS therefore duramycin was conjugated to a porphyrin based PS which was achieved via direct reaction with the ε-amino group on the lysine residue near duramycin's N-terminal. The compound was subsequently purified using RP-HPLC and confirmed using mass spectrometry. Binding of the conjugate to ovarian and pancreatic cancer cell lines was assessed by flow cytometry. Light irradiation with a light fluence of 7.5 J/cm² was delivered to conjugate treated cancer cells and cell proliferation analysed by MTT assay. The conjugate detected PE on all 4 cancer cell lines in a concentration dependent manner and conjugate plus irradiation effectively reduced cell proliferation at concentrations ≥ 0.5 μM, dependent on cancer cell line. Reduction in cell proliferation by the irradiated conjugate was enhanced over unconjugated duramycin in A2780, AsPC-1 and SK-OV-3 (p < 0.05). In this study we have shown that a duramycin-porphyrin conjugate retained good binding affinity for its target and, following irradiation, reduced cell proliferation of pancreatic and ovarian cancer cell lines.

Citation

Broughton, L. J., Giuntini, F., Savoie, H., Bryden, F., Boyle, R. W., Maraveyas, A., & Madden, L. A. (2016). Duramycin-porphyrin conjugates for targeting of tumour cells using photodynamic therapy. Journal of photochemistry and photobiology. B, Biology, 163, 374-384. https://doi.org/10.1016/j.jphotobiol.2016.09.001

• Acceptance Date: Sep 1, 2016
• Online Publication Date: Sep 3, 2016
• Publication Date: 2016-10
• Deposit Date: Sep 14, 2016
• Publicly Available Date: Sep 14, 2016
• Journal: Journal of photochemistry and photobiology B : biology
• Print ISSN: 1011-1344
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 163
• Pages: 374-384
• DOI: https://doi.org/10.1016/j.jphotobiol.2016.09.001
• Keywords: Duramycin; Porphyrin; Photodynamic therapy; Cancer; Phosphatidylethanolamine
• Public URL: https://hull-repository.worktribe.com/output/443031
• Publisher URL: http://www.sciencedirect.com/science/article/pii/S1011134416304778
• Additional Information: This article is maintained by: Elsevier; Article Title: Duramycin-porphyrin conjugates for targeting of tumour cells using photodynamic therapy; Journal Title: Journal of Photochemistry and Photobiology B: Biology; CrossRef DOI link to publisher maintained version: http://dx.doi.org/10.1016/j.jphotobiol.2016.09.001; Content Type: article; Copyright: © 2016 Elsevier B.V. All rights reserved.
• Contract Date: Sep 14, 2016