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

Broughton, LJ and Giuntini, F and Savoie, H and Bryden, F and Boyle, RW and Maraveyas, A and Madden, LA (2016) Duramycin-porphyrin conjugates for targeting of tumour cells using photodynamic therapy. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 163. pp. 374-384. ISSN 1011-1344

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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 b 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.

Item Type: Article
Uncontrolled Keywords: 0601 Biochemistry And Cell Biology, 0299 Other Physical Sciences
Subjects: Q Science > QD Chemistry
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: ELSEVIER SCIENCE SA
Related URLs:
Date Deposited: 22 Dec 2016 10:48
Last Modified: 03 Sep 2017 23:50
DOI or Identification number: 10.1016/j.jphotobiol.2016.09.001
URI: http://researchonline.ljmu.ac.uk/id/eprint/5064

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