Drug delivery


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Project introduction

Nitroreductases are enzymes of which the true biological roles are still being elucidated, but have the ability to react with nitro-groups either on explosives or prodrugs, and are thus of interest for explosive detection, bioremediation and cancer prodrug therapy.

This project has its interests in cancer prodrug therapy (chemotherapy) specifically, a novel method to deliver nitroreductases to solid tumours. The novel method is based on the use of gold-coated magnetic nanoparticles (Au-MNPs) as a delivery vehicle for bacterial nitroreductases to solid tumours using a focused magnetic beam. This method hopes to overcome the current limitation of poor enzyme expression and inefficient tumour targeting.

Importantly, the Au-MNPs required for this project cannot be obtained commercially, and we have optimised a method to synthesise these in-house. One branch of this research is further optimisation of the current protocol as well as producing particles of various sizes. Also, the identification and expression of known and novel nitroreductases are an on-going activity in order to select enzymes with greater efficiency than the most studied NfnB from E. coli. This work includes characterising novel enzymes and their enzyme products using HPLC and NMR. We are also investigating the cytotoxicity of enzyme-nanoparticle conjugates on cancer cell lines in order to select the best combinations for testing in mouse trials. Last but not least, we aim to determine the nanotoxicology (biodegradation, elimination, distribution, etc.) of the bare and conjugated nanoparticles. Understanding the impact of nanoparticles is part of the recommendations made by the House of Lords Science and Technology select committee.

References

  • Drug activation carrier, WO2011026898-A2; WO2011026898-A3; EP2473197-A2; US2012232328-A1; EP2473197B
  • V. V. Gwenin, P. Paramasivan, J. Halliwell, P. Ball, G. Robinson, C. D. Gwenin, Identification of novel nitroreductases from Bacillus cereus and their interaction with the CB1954 prodrug, Biochemical Pharmacology, 98 392-402 (2015) DOI: 10.1016/j.bcp.2015.09.01
  • V. V. Gwenin, C. D. Gwenin, M. Kalaji, Colloidal gold modified with a genetically engineered nitroreductase: Towards a novel enzyme delivery system for cancer prodrug therapy. Langmuir, 2011, 27, 14300 DOI: 10.1021/la202951p

Gwenin - Applied Research in Chemistry and Public Health (ARCH)

Gwenin - Applied Research in Chemistry and Public Health (ARCH)

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Gwenin - Applied Research in Chemistry and Public Health (ARCH)

College of Environmental Sciences and Engineering, Bangor University, Bangor, Gwynedd, LL57 2DG, UK

Direct Line: 0044 1248 383741   email: c.d.gwenin@bangor.ac.uk

Gwenin - Applied Research in Chemistry and Public Health (ARCH)

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News: August 2018

Congratulations to Nagina Kanwal who joins us from Pakistan

Nagina Kanwal

News: June 2018

We presented at the North Wales Clinical Research Centre Conference

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News: June 2018

Congratulations to Mohammad Rizwan who will be joining us on the CALIN project from August

Mohammad Rizwan

News: May 2018

Alice held a successful CALIN PhD forum

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News: May 2018

CarolCarol Thomas joins our team