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.

Westminster experience had by 1973 evolved the concept of displacement bone marrow transplantation and extended the donors from matched siblings to other family [48] and unrelated [4] donors. The principles of its use to install donor bone marrow as a component factory for the life of the recipient, together with the importance of immunoprophylaxis are detailed. Satisfying correction has been achieved for 48 previously fatal genetic diseases, partial correction for another 5 with failure for 3 diseases. Displacement bone marrow transplantation is not a panacea, but could be applied to about 7% of known inborn errors, devising in vitro tests which can predict in vivo donor effects, especially since some 80% of our patients are not found in known families and could not have been prevented.

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