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Details of Grant 

EPSRC Reference: EP/M008657/1
Title: Engineering Multi-functional Nanomaterials to Treat Metastatic Cancer
Principal Investigator: Al-Jamal, Dr W
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Kings College London Queen Mary University of London UCL
Department: Pharmacy
Organisation: University of East Anglia
Scheme: First Grant - Revised 2009
Starts: 18 May 2015 Ends: 21 July 2017 Value (£): 99,870
EPSRC Research Topic Classifications:
Drug Formulation & Delivery Materials Synthesis & Growth
EPSRC Industrial Sector Classifications:
Healthcare
Related Grants:
Panel History:
Panel DatePanel NameOutcome
23 Jul 2014 EPSRC Physical Sciences Materials - July 2014 Announced
Summary on Grant Application Form
Prostate cancer is the most common type of cancer and the second most common cause of death in men in the UK. Cancer metastasis (cancer cells spread outside the primary tumour) is the most serious complication of prostate cancer, with median patient survival of 12-18 months with current available chemotherapeutics. Chemotherapy is an approach which utilises anti-cancer drugs for killing tumour cells however it is associated with undesirable side effects due to its acting on normal healthy cells. Following systemic administration, cytotoxic drugs are eliminated rapidly from the blood stream which results in poor drug accumulation at metastatic cancer lesions. To overcome these shortcomings, drugs have been encapsulated into ultra-small objects called "nanocarriers". Liposomes are one example of these nanocarriers, made of natural lipid composition thus considered as the safest nanocarrier systems developed so far. Encapsulation of drugs into liposomes prolongs their residency time in the blood by decreasing their renal and hepatic clearance. In addition, drug-loaded nanocarriers will utilise the tumour leaky vasculature, known as enhanced permeation and retention (EPR) effect, to improve drug delivery to cancer cells. However, the poor release of the drug from such nanocarriers is considered the main challenge in cancer drug delivery. In this proposal we describe the development of targeted delivery systems that recognise prostate cancer cells, and efficiently release the encapsulated chemotherapeutics in response to an externally applied magnetic field. Such an approach aims to increase drug accumulation at the tumour tissues, and reduce undesirable systemic side effects. The targeting ligand was chosen to recognise only prostate cancer cells as this targeting moiety recognises specific proteins (called PSMA) only expressed on this cell type thus sparing healthy tissues. To overcome the poor release of the drug, temperature-sensitive liposomes (TSL) will be formulated so that they "break down" and release the drug only at temperatures higher than the body temperature (i.e.42C). The temperature-sensitive liposomes will be developed by incorporating magnetic iron oxide nanoparticles inside the liposomes besides the anticancer drug. The magnetic nanoparticles will heat when exposed to a "safe" alternating magnetic field so that the drug can be released from the TSL. At the same time the magnetic nanoparticles will act as "imaging agents" so their accumulation in the tumour will be visualized by Magnetic Resonance Imaging (MRI). This proposal aims to translate our innovative delivery system as a potential therapy for metastatic prostate cancer. It is anticipated that safer and more effective targeted nanocarriers will emerge to treat metastatic prostate cancer so that chemotherapy side effects are hugely reduced.
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