Nanoparticle paves the way for new triple negative breast cancer drug

Breast cancer drug

Published on 17 March 2017

A Sunderland academic’s research has supported the development of a potential new drug which tackles the highly aggressive ‘triple negative’ breast cancer – and a nanoparticle to deliver it directly into the cancer cells.

The drug is a peptide (fragment of a protein) discovered by Professor Mohamed El-Tanani at the University of Bradford’s Institute for Cancer Therapeutics. Professor El-Tanani has shown in computer models that the peptide blocks a protein called RAN which helps cancer cells to divide and grow. High levels of RAN have been linked to aggressive tumour growth, cancer spread, resistance to chemotherapy and poor prognosis in a number of cancers, including triple negative breast cancer (TNBC).

Professor Mohamed El-Tanani is working with Dr Ahmed Faheem, a Senior Lecturer in Pharmaceutics in the University of Sunderland’s Faculty of Health Sciences and Wellbeing.

Prof El-Tanani explained: “We knew we’d need a novel delivery mechanism for this drug because peptides on their own are unstable and they can degrade too quickly to be effective. Using a nanoparticle as a delivery mechanism was the perfect solution.”

The team, which also includes Ulster University, and Queen’s University Belfast, developed a nanoparticle from a biodegradable polymer that could encapsulate the peptide. They tested various different polymers in order to determine which was most effective at helping the protein enter the cancer cells and attack them.

“By developing a nanoparticle that can help this peptide enter triple negative breast cancer cells and block RAN, we’ve brought this potential new treatment a step closer to the clinic."

Laboratory tests showed that when this nanoparticle, loaded with the peptide, was added to the triple negative breast cancer cells, the cells would actively take it in. Their growth rate then reduced, they stopped replicating and around two thirds of the cells died within 24 hours. This compared with the peptide on its own, or an empty nanoparticle, which had no impact on the cells’ growth.

The researchers also confirmed that the drug was killing the cancer cells through the mechanism they had seen in their computer models – by blocking the action of RAN which plays an important role in cell division and growth. Previous research by Professor El-Tanani has shown that blocking RAN can also prevent or even reverse resistance to chemotherapy in small cell lung cancer (link is external).

Between 10-20 percent of breast cancers are found to be triple negative – which means the cancer does not have receptors for the hormones oestrogen and progesterone or the protein HER2. This limits the range of treatments that can be used, resulting in poorer prognosis and increased risk of recurrence.

Dr Faheem said: “Once contacted by Prof El-Tanani regarding the potential of the new peptide and the obstacles facing its cellular uptake, I utilised my research expertise in the area of formulation of biodegradable nano-particles for peptide delivery, to develop a strategy for engineering and full characterisation of a plethora of nano-particles to be tested in his lab for its biological activity against cancer.”   

“By developing a nanoparticle that can help this peptide enter triple negative breast cancer cells and block RAN we’ve brought this potential new treatment a step closer to the clinic,” said Professor El-Tanani. “We’re already working on in vivo tests of the nanoparticle in a triple negative breast cancer model and are thinking ahead to taking this drug into clinical trials.”

Professor El-Tanani is also working on a number of other potential RAN inhibitors, including a ‘repurposed’ drug that has been already pre-clinically validated in breast and lung cancer and is ready for clinical trials. The University of Bradford is  actively seeking further funding and investor support to support the development of these drug candidates.

Dr Ahmed Faheem

Dr Ahmed Faheem is a Senior Lecturer in Pharmaceutics at Sunderland Pharmacy School. He graduated from the University of Tanta, Egypt, with a BSc (Hons) in Pharmaceutical Sciences, and then obtained an MSc in Pharmaceutical Technology. He gained his PhD in Drug Delivery and Targeting from London School of Pharmacy (currently UCL School of Pharmacy) in 2006. He then undertook postdoctoral positions investigating drug delivery systems for pulmonary delivery of anticancer medicines at Strathclyde Institute of Pharmacy and Biomedical Sciences, and for controlled delivery of HIV microbicides at Queen’s University Belfast.

He was appointed as a lecturer at Ulster University in 2009 and made a substantial contribution in the area of Pharmaceutics towards the development of the MPharm degree programme and played a key role in establishing a new School of Pharmacy and Pharmaceutical Sciences. From 2010 till 2015, he was the Course Director for MSc in Pharmaceutical Sciences at Ulster.

His research interests focuses on the use of biodegradable nanoparticles for peptide and siRNA delivery and targeting including antidiabetic and antimetastatic peptides; vaccine delivery and targeting and pulmonary delivery of drugs and peptides.

Dr Faheem has established collaborative links with a number of national and international research groups and he has taken a leading role in developing international relations with academic partners for the University of Sunderland.