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Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy

Simon D. Anderson, Robert Hobbs, Vanessa V. Gwenin , Patrick Ball, Lindsey A. Bennie , Jonathan A. Coulter , Chris D. Gwenin

Journal of Functional Biomaterials, Volume: 10, Issue: 4, Start page: 45

Swansea University Author: Robert Hobbs

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DOI (Published version): 10.3390/jfb10040045

Abstract

Directed enzyme prodrug therapy (DEPT) involves the delivery of a prodrug-activating enzyme to a solid tumour site, followed by the subsequent activation of an administered prodrug. One of the most studied enzyme–prodrug combinations is the nitroreductase from Escherichia coli (NfnB) with the prodru...

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Published in: Journal of Functional Biomaterials
ISSN: 2079-4983
Published: MDPI AG 2019
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URI: https://cronfa.swan.ac.uk/Record/cronfa54443
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spelling 2021-08-18T14:44:22.2357126 v2 54443 2019-09-30 Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy aa993b1fe49241b9938dfb43633b5859 Robert Hobbs Robert Hobbs true false 2019-09-30 EEN Directed enzyme prodrug therapy (DEPT) involves the delivery of a prodrug-activating enzyme to a solid tumour site, followed by the subsequent activation of an administered prodrug. One of the most studied enzyme–prodrug combinations is the nitroreductase from Escherichia coli (NfnB) with the prodrug CB1954 [5-(aziridin-1-yl)-2,4-dinitro-benzamide]. One of the major issues faced by DEPT is the ability to successfully internalize the enzyme into the target cells. NfnB has previously been genetically modified to contain cysteine residues (NfnB-Cys) which bind to gold nanoparticles for a novel DEPT therapy called magnetic nanoparticle directed enzyme prodrug therapy (MNDEPT). One cellular internalisation method is the use of cell-penetrating peptides (CPPs), which aid cellular internalization of cargo. Here the cell-penetrating peptides: HR9 and Pep-1 were tested for their ability to conjugate with NfnB-Cys. The conjugates were further tested for their potential use in MNDEPT, as well as conjugating with the delivery vector intended for use in MNDEPT and tested for the vectors capability to penetrate into cells. Journal Article Journal of Functional Biomaterials 10 4 45 MDPI AG 2079-4983 nitroreductase; cell-penetrating peptide; prodrug therapy; darkfield imaging; nanoparticle 1 10 2019 2019-10-01 10.3390/jfb10040045 COLLEGE NANME Engineering COLLEGE CODE EEN Swansea University 2021-08-18T14:44:22.2357126 2019-09-30T00:00:00.0000000 Professional Services ISS - Uncategorised Simon D. Anderson 1 Robert Hobbs 2 Vanessa V. Gwenin 3 Patrick Ball 4 Lindsey A. Bennie 5 Jonathan A. Coulter 6 Chris D. Gwenin 7 54443__20660__a75cdddcc6d24329b6786a4a7bfc956a.pdf 54443.pdf 2021-08-18T14:43:20.7889127 Output 5889741 application/pdf Version of Record true © 2019 by the authors. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) license true eng http://creativecommons.org/licenses/by/4.0/
title Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy
spellingShingle Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy
Robert Hobbs
title_short Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy
title_full Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy
title_fullStr Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy
title_full_unstemmed Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy
title_sort Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy
author_id_str_mv aa993b1fe49241b9938dfb43633b5859
author_id_fullname_str_mv aa993b1fe49241b9938dfb43633b5859_***_Robert Hobbs
author Robert Hobbs
author2 Simon D. Anderson
Robert Hobbs
Vanessa V. Gwenin
Patrick Ball
Lindsey A. Bennie
Jonathan A. Coulter
Chris D. Gwenin
format Journal article
container_title Journal of Functional Biomaterials
container_volume 10
container_issue 4
container_start_page 45
publishDate 2019
institution Swansea University
issn 2079-4983
doi_str_mv 10.3390/jfb10040045
publisher MDPI AG
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hierarchy_top_title Professional Services
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description Directed enzyme prodrug therapy (DEPT) involves the delivery of a prodrug-activating enzyme to a solid tumour site, followed by the subsequent activation of an administered prodrug. One of the most studied enzyme–prodrug combinations is the nitroreductase from Escherichia coli (NfnB) with the prodrug CB1954 [5-(aziridin-1-yl)-2,4-dinitro-benzamide]. One of the major issues faced by DEPT is the ability to successfully internalize the enzyme into the target cells. NfnB has previously been genetically modified to contain cysteine residues (NfnB-Cys) which bind to gold nanoparticles for a novel DEPT therapy called magnetic nanoparticle directed enzyme prodrug therapy (MNDEPT). One cellular internalisation method is the use of cell-penetrating peptides (CPPs), which aid cellular internalization of cargo. Here the cell-penetrating peptides: HR9 and Pep-1 were tested for their ability to conjugate with NfnB-Cys. The conjugates were further tested for their potential use in MNDEPT, as well as conjugating with the delivery vector intended for use in MNDEPT and tested for the vectors capability to penetrate into cells.
published_date 2019-10-01T04:07:59Z
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score 11.016302

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