Rose Bengal-Amphiphilic Peptide Conjugate for enhanced Photodynamic therapy for malignant melanoma

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Abstract

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.
LanguageEnglish
Pages1328
Number of pages9
JournalJournal of Medicinal Chemistry
Volume63
Issue number3
Early online date15 Jan 2020
DOIs
Publication statusPublished - 13 Feb 2020

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Rose Bengal
Photochemotherapy
Melanoma
Peptides
Reactive Oxygen Species
Proto-Oncogene Proteins c-akt
Survival
Protein-Serine-Threonine Kinases
Skin Neoplasms
Oxidative Stress
KLA peptide
Therapeutics
Neoplasms

Cite this

@article{bbd4f26061db43fdaf373994fdb76119,
title = "Rose Bengal-Amphiphilic Peptide Conjugate for enhanced Photodynamic therapy for malignant melanoma",
abstract = "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.",
author = "Simon Porter and Yingjie Sheng and McHale, {Anthony P.} and J Callan and Heather Nesbitt and Thomas McKaig and Kathryn Burnett and Bronagh White and Matin, {Rubeta N.} and Bridgeen Callan",
year = "2020",
month = "2",
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doi = "10.1021/acs.jmedchem.9b01802",
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journal = "Journal of Medicinal Chemistry",
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TY - JOUR

T1 - Rose Bengal-Amphiphilic Peptide Conjugate for enhanced Photodynamic therapy for malignant melanoma

AU - Porter, Simon

AU - Sheng, Yingjie

AU - McHale, Anthony P.

AU - Callan, J

AU - Nesbitt, Heather

AU - McKaig, Thomas

AU - Burnett, Kathryn

AU - White, Bronagh

AU - Matin, Rubeta N.

AU - Callan, Bridgeen

PY - 2020/2/13

Y1 - 2020/2/13

N2 - 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.

AB - 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.

U2 - 10.1021/acs.jmedchem.9b01802

DO - 10.1021/acs.jmedchem.9b01802

M3 - Article

VL - 63

SP - 1328

JO - Journal of Medicinal Chemistry

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JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 3

ER -