New approaches for improved stent patency and tumour cell killing

About the Project

Cholangiocarcinoma (CCA), or cancer of the biliary tract, affects around 3000 people in the UK each year; CCA incidence and mortality are increasing and recent findings indicate that mortality is now equal that of hepatocellular carcinoma (HCC). Often diagnosed at a late stage, CCA has a dismal prognosis with only 13% of patients surviving 3 years. CCA generally presents with narrowed bile segments (strictures) of the bile ducts without specific, diagnostic imaging features. Opening a bile duct blockage by inserting a stent (a metal or plastic tube) is necessary in the majority of patients before surgery or chemotherapy (and to avoid infection of the stagnant bile). A problem with stenting is that tumour in-growth often occludes the stent resulting in the need for re-stenting; biliary sludge (bacterial growth and protein deposition) also contributes to stent occlusion. New treatment modalities that can occur alongside stenting would be of great value. Moreover, any drug treatments that maintain stent patency would also be of great benefit to patients to avoid repeated surgery. This project primarily seeks to develop biomaterials and drugs that will allow an increase in stent patency in CCA.

Drug eluting stents are in development for biliary tract cancer. Gemcitabine (GEM) with Cisplatin (CIS) is known to be a potent treatment for CCA that improves survival. A nanofibre membrane releasing GEM and/or CIS was used to coat a metal stent. This novel membrane covered biliary stent showed a sustained local drug release and potent anti-tumor activity in vitro and in vivo in  bile duct models.

In this project we will be developing novel stents that incorporate bio-instructive polymers to inhibit bacterial biofilm growth on the stent and to release novel drugs that can inhibit bile duct tumour growth. We will also investigate incorporation of microparticles (produced using microfluidics) to release drugs from the stent. The microparticles will be of different kinds -those able to hydrolytically degrade with time to release tumour cell inhibitory compounds and -those that remain undegraded to contain molecules that promote bacterial growth inhibition. The effect of the polymer-drug conjugates and the microparticles will be examined in bacterial and mammalian cells. Additionally this project will seek to develop ex vivo bile duct models for modelling the effect of the polymer-drug conjugates on normal cells. Therefore this project is highly interdisciplinary in nature and this is reflected in the supervisory team.

Funding Notes

Funding: AMMF/UON

We will consider applications from prospective students with:

• a good biomedical or related degree,
• Masters in Chemistry or Cancer Biology, Natural Sciences or Biochemistry or with related degree,
• a good command of the English language (written and spoken) as outlined in the postgraduate prospectus,
• competence with computers and data handling,

To be considered for this studentship, please apply online at: View Website

Please note this application is only for UK students. Standard UK stipend available for 3 years.

Please include in your application:

• A detailed CV;
• Names and addresses of three referees;
• A covering letter highlighting your research experience/capabilities;