A New Drug and Nanoparticle Combination for Triple Negative Breast Cancer

Professor Mohamed El-Tanani, Institute for Cancer Therapeutics, University of Bradford, UK. CREDIT: University of Bradford.

A research team from the UK has developed a prospective new drug for confronting the highly aggressive “triple negative” breast cancer (TNBC), as well as a nanoparticle for delivering the drug directly into the cancer cells.

Professor Mohamed El-Tanani from the Institute for Cancer Therapeutics at the University of Bradford has discovered the new drug, which is a peptide, that is, a protein fragment. Professor El-Tanani has demonstrated, using computer models, that the peptide inhibits a protein known as RAN which helps the division and growth of cancer cells.

Higher levels of RAN are known to cause aggressive growth of tumor, spreading of cancer, resistance to chemotherapy, and poor prognosis in many types of cancers, such as the TNBC.

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.

Professor Mohamed El-Tanani, University of Bradford

The research team worked in collaboration with researchers from Ulster University, Sunderland, and Queen’s University Belfast to develop a nanoparticle with the ability to encapsulate the peptide. The nanoparticle was made of a biodegradable polymer.

The researchers analyzed a number of different polymers to determine the most effective nanoparticle that could help the entry of the protein into the cancer cells to attack the cancer cells.

Laboratory tests demonstrated that when the nanoparticle that included the peptide was added to the TNBC cells, the cells actively took it in. Consequently, the growth rate of the cancer cells reduced, their replication stopped, and nearly two-thirds of the cancer cells died within a time period of 24 hours. The researchers compared the effect of this with the addition of just the peptide, or an empty nanoparticle, which did not have any effect on the growth of the cells.

The research team also validated the point that the drug destroyed the cancer cells through the same mechanism that they had viewed in the computer models, that is, it blocked the action of RAN which has a significant role in the division and growth of the cancer cells.

Prior research carried out by Professor El-Tanani has indicated that when RAN is blocked, the resistance to chemotherapy in small cell lung cancer can be prevented or even reversed.

Almost 10% - 20% of breast cancers are known to be triple negative. This implies that this type of cancer does not have any receptors neither for the progesterone or estrogen hormones nor for the protein HER2, limiting the array of treatments available, and hence leading to poorer prognosis and heightened recurrence risk.

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. 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 Mohamed El-Tanani, University of Bradford

Professor El-Tanani has also been researching on a range of other probable RAN inhibitors, which include a “repurposed” drug already pre-clinically validated in lung and breast cancer and now ready for clinical trials. The University of Bradford has been actively soliciting additional investor support and funding to aid the development of such drugs.

The outcomes of this research have been published in the International Journal of Pharmaceutics.

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