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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

1
School of Natural Sciences, Bangor University, Bangor, Gwynedd, Wales LL57 2DG, UK
2
School of Pharmacy, Queen’s University Belfast, Belfast BT7 1NN, UK
*
Author to whom correspondence should be addressed.
J. Funct. Biomater. 2019, 10(4), 45; https://doi.org/10.3390/jfb10040045
Received: 16 August 2019 / Revised: 30 September 2019 / Accepted: 30 September 2019 / Published: 1 October 2019
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. View Full-Text
Keywords: nitroreductase; cell-penetrating peptide; prodrug therapy; darkfield imaging; nanoparticle nitroreductase; cell-penetrating peptide; prodrug therapy; darkfield imaging; nanoparticle
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Anderson, S.D.; Hobbs, R.J.; Gwenin, V.V.; Ball, P.; Bennie, L.A.; Coulter, J.A.; Gwenin, C.D. Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy. J. Funct. Biomater. 2019, 10, 45.

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