A universal magnetic carrier for use in cancer prodrug therapy

• Main Author: Hobbs, Robert John
• Published: Bangor University 2015
• Subjects: 616.99
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.698922

Magnetic nanoparticles have attracted huge amounts of interest in the scientific and healthcare communities. Fe3O4 and γ-Fe2O3 are magnetic nanoparticles of particular interest in nanotherapeutics and have already been approved for use by the Medicines and Healthcare Products Regulatory Agency along with the United States Food and Drug Administration. Magnetic nanoparticle directed enzyme prodrug therapy is a novel drug delivery system being developed in this project to allow targeted cancer treatment. Magnetic nanoparticle directed enzyme prodrug therapy hopes to utilise gold coated magnetic nanoparticles to deliver nitroreductases; immobilised to the particle surface, to the tumour site under a magnetic field. At the tumour site the nitroreductases will convert prodrugs into their active cytotoxic forms destroying the tumour cells. Gold coated magnetic nanoparticles have been successfully synthesized and the previously modified nitroreductases; NfsB and YfkO in both a –His and –Cys tagged form were expressed and purified. The nitroreductase YfkO-cys was then immobilised onto the synthesised gold coated magnetic nanoparticles via gold-thiol bonds. The YfkO-cys retained its enzymatic activity towards the prodrug CB1954 whilst conjugated to the particles and this is believed to be the first successful attempt and report of this system. Furthermore the genetically modified nitroreductase NfsB-cys has been tested on a cell line in vitro. Using a combination treatment of nitroreductase (200 nM), cofactor NADH and the prodrug CB1954 (10 μM) the system exhibited an average cell survival rate of ~ 20%.