New drug delivery could significantly improve treatment outcomes for localised prostate cancer
Researchers at Queen’s University Belfast have developed a new treatment to be used in combination with radiotherapy that could significantly improve treatment outcomes for men with locally advanced prostate cancer.
The treatment can make cancerous cells up to 30% more receptive to radiotherapy while simultaneously reducing adverse side effects that limit quality of life.
Radiotherapy is extensively used to treat various localised cancers including prostate cancer, offering the best chance for curative intervention. However, approximately 30% of prostate cancer patients experience treatment failure leading to disease progression.
The research team at Queen’s have developed a new nanomedicine comprised of tiny gold particles, coated in a small peptide called RALA. If these nanoparticles are present in tumour cells when treated with radiotherapy, they increase the cell killing potential of this conventional treatment, helping to reduce the risk of disease relapse. In the absence of radiation, the gold nanoparticles are not directly toxic, meaning that risk of treatment related toxicity is low.
Various groups around the world have reported that gold nanoparticles, or other high-atomic number elements, hold the potential to sensitise tumour cells to radiation treatment, but one key challenge has been delivering these particles in sufficient levels to the right regions within the tumour cells. Combining the gold particles with RALA increases the efficiency of nanoparticle uptake, while also enabling the gold particles to be delivered to regions within the cells which are more sensitive to the effects of radiation damage.
The study, published in Nanobiotechnology, highlights that through the new formulation, prostate cancer cells were rendered up to 30% more sensitive to the cell killing effects of the same radiotherapy used to treat patients. Furthermore, in experiments investigating the magnitude of effect in small 3-dimentional models of prostate tumors called tumourspheres, the combination of radiation and RALA-gold nanoparticles completely suppressed tumoursphere growth.
Professor Helen McCarthy, from the School of Pharmacy at Queen’s University Belfast, explains: “The peptide enables the gold nanoparticles to be delivered more efficiently to the tumour cells. The gold then interacts with the radiotherapy, increasing the cell killing effect in a highly localised manner.”
The gold particles are up to three times more visible on standard medical imaging equipment. This means that if the nanoparticles are located within the tumour, they should help to improve the accuracy of radiotherapy delivery, reducing the risk of off-target damage to neighboring normal tissue such as the bladder or bowel.
Dr Jonathan Coulter explains: “Our research has shown that ultra-low concentrations of the RALA-gold nanoparticles effectively sensitise prostate tumour cells to radiotherapy. Now we want to build on this work, to address the second major challenge, consistently delivering sufficient nanoparticles to the tumour throughout a patients’ radiotherapy. We are delighted to report that Prostate Cancer UK are supporting our proposal to develop a biodegradable implant designed to provide sustained release of the gold nanoparticles.”
“Following insertion into the main tumour lesion, the biodegradable implant will consistently release the nanoparticles over time. This is opposed to current approaches that involve daily injections. Following consultation with a local prostate cancer patient focus groups, we learned that a one off implant would be better tolerated by patients than regular injections to the tumour.”
Dr Coulter and an extended multi-disciplinary team (Professor Jain, Professor McCarthy, Professor Donnelly, Dr Larrañeta and Dr McMahon) have recently been awarded £376,000 from Prostate Cancer UK to evaluate the effectiveness of these implants at increasing the sensitivity of prostate cancer cells to radiotherapy.