Rose Bengal-Amphiphilic Peptide Conjugate for Enhanced Photodynamic Therapy of Malignant Melanoma

Simanpreet Kaur Dhillon, Simon Porter, Nermeen Rizk, Yingjie Sheng, Thomas McKaig, Kathryn Burnett, Bronagh White, Heather Nesbitt, Rubeta N. Matin, Anthony P. McHale, Bridgeen Callan, J Callan

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28 Citations (Scopus)
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Malignant melanoma is an aggressive skin cancer with poor survival outcomes for patients diagnosed at an advanced stage. While targeted serine/threonine-protein kinase B-Raf (BRAF) and immune checkpoint inhibitors have improved survival outcomes for a proportion of these patients, response rates remain variable. There is a need, therefore, for more effective treatments to bolster the options available for melanoma patients. In this manuscript, we covalently attached Rose Bengal (RB) to the amphipathic peptide (AMP) C(KLAKLAK)2 and determined the effectiveness of the resulting RB-C(KLAKLAK)2 conjugate as a photodynamic therapy (PDT) sensitizer. RB-C(KLAKLAK)2-mediated PDT treatment of subcutaneous B16-F10-Luc2 tumors in C57 mice resulted in lesions that were 479% smaller at the end of the study than animals treated with RB-mediated PDT. The synergistic effect between RB and C(KLAKLAK)2 has been attributed to the AMP sensitizing cells to reactive oxygen species (ROS), making them more susceptible to ROS-induced oxidative stress.
Original languageEnglish
Pages (from-to)1328-1336
Number of pages9
JournalJournal of Medicinal Chemistry
Issue number3
Early online date15 Jan 2020
Publication statusPublished (in print/issue) - 13 Feb 2020

Bibliographical note

Funding Information:
S.L.P. acknowledges support from Invest NI under their Proof of Concept Scheme. S.K.D. acknowledges support from the Royal Society under their Newton Fellowship scheme.

Publisher Copyright:
Copyright © 2020 American Chemical Society.

Copyright 2020 Elsevier B.V., All rights reserved.


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