Development of Gold Coated Superparamagnetic Iron Oxide Nanoparticles for Nitroreductase Delivery

M.P. Cude; C.D. Gwenin

doi:10.1149/1.3583517

Development of Gold Coated Superparamagnetic Iron Oxide Nanoparticles for Nitroreductase Delivery

M.P. Cude, C.D. Gwenin

Engineering and Physical Sciences Research Council (ESPRC)

Research output: Contribution to journal › Article › peer-review

Abstract

Directed enzyme prodrug therapies (DEPT) currently suffer from inherent problems associated with localising and retaining enzymes at tumours. Superparamagnetic iron oxide nanoparticles (SPION) have been synthesised (≈10 nm) and surface functionalised with gold by direct reduction and by attachment of pre-synthesised Au seeds; these Au-SPION sols are stable in aqueous solution and are susceptible to magnetic manipulation. We have genetically modified the nitroreductase (NTR) yfkO from Bacillus Licheniformis to include a sequence of 12 cysteine residues, this modified NTR retains activity with CB1954 and has been immobilised onto gold via the 12 Au-S bonds. The yfkO-cys12 can therefore be immobilised with controlled orientation onto the Au-SPION to allow a magnetically directed enzyme prodrug therapy (MDEPT) to be developed; creating a novel strategy to target and localise prodrug activation to cancer tumour sites using magnetism.

Original language	English
Pages (from-to)	79-89
Journal	ECS Transactions
Volume	33
Issue number	38
DOIs	https://doi.org/10.1149/1.3583517
Publication status	Published - 1 Jan 2011

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title = "Development of Gold Coated Superparamagnetic Iron Oxide Nanoparticles for Nitroreductase Delivery",

abstract = "Directed enzyme prodrug therapies (DEPT) currently suffer from inherent problems associated with localising and retaining enzymes at tumours. Superparamagnetic iron oxide nanoparticles (SPION) have been synthesised (≈10 nm) and surface functionalised with gold by direct reduction and by attachment of pre-synthesised Au seeds; these Au-SPION sols are stable in aqueous solution and are susceptible to magnetic manipulation. We have genetically modified the nitroreductase (NTR) yfkO from Bacillus Licheniformis to include a sequence of 12 cysteine residues, this modified NTR retains activity with CB1954 and has been immobilised onto gold via the 12 Au-S bonds. The yfkO-cys12 can therefore be immobilised with controlled orientation onto the Au-SPION to allow a magnetically directed enzyme prodrug therapy (MDEPT) to be developed; creating a novel strategy to target and localise prodrug activation to cancer tumour sites using magnetism.",

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AB - Directed enzyme prodrug therapies (DEPT) currently suffer from inherent problems associated with localising and retaining enzymes at tumours. Superparamagnetic iron oxide nanoparticles (SPION) have been synthesised (≈10 nm) and surface functionalised with gold by direct reduction and by attachment of pre-synthesised Au seeds; these Au-SPION sols are stable in aqueous solution and are susceptible to magnetic manipulation. We have genetically modified the nitroreductase (NTR) yfkO from Bacillus Licheniformis to include a sequence of 12 cysteine residues, this modified NTR retains activity with CB1954 and has been immobilised onto gold via the 12 Au-S bonds. The yfkO-cys12 can therefore be immobilised with controlled orientation onto the Au-SPION to allow a magnetically directed enzyme prodrug therapy (MDEPT) to be developed; creating a novel strategy to target and localise prodrug activation to cancer tumour sites using magnetism.

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Development of Gold Coated Superparamagnetic Iron Oxide Nanoparticles for Nitroreductase Delivery

Abstract

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