TY - JOUR

T1 - Cell Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy

AU - Anderson, Simon D.

AU - Hobbs, Robert J.

AU - Gwenin, Vanessa V.

AU - Ball, Patrick

AU - Bennie, Lindsey A.

AU - Coulter, Jonathan C.

AU - Gwenin, Chris D.

PY - 2019/12

Y1 - 2019/12

N2 - 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 Pep1 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

AB - 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 Pep1 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

KW - cell-penetrating peptide

KW - darkfield imaging

KW - nanoparticle

KW - nitroreductase

KW - prodrug therapy

U2 - 10.3390/jfb10040045

DO - 10.3390/jfb10040045

M3 - Article

C2 - 31581475

VL - 10

JO - Journal of Functional Biomaterials.

JF - Journal of Functional Biomaterials.

SN - 2079-4983

IS - 4

ER -