The combination of chemo and radiotherapy has been shown to be highly effective in the treatment of muscle invasive bladder cancer. However, the side-effects associated with this treatment can be debilitating and, in many cases, prevent treatment from being successful. A collaborative project between our team and the Department of Oncology has sought to address this challenge by loading chemotherapy drugs into microbubbles. Since ultrasound can be tightly focused deep within the body, drug release can be localised to the site of the tumour. We have shown that the drug-loaded bubbles can produce the same effect as systemically administered chemotherapy in an orthotopic tumour model, but with significantly lower doses and minimal toxicity.
Cancer cells following fusion with drug-loaded microbubbles
Pancreatic adenocarcinoma remains one of the most lethal forms of cancer. Treatment options are severely limited by the fact that patients are often only diagnosed when tumours have progressed to an advanced stage and aggressive chemo or radiotherapy cannot be tolerated.
Using stimuli responsive systems to localise drug release can substantially reduce off-target effects. It cannot, however, eliminate them, as some drug will inevitably be taken up in the liver and kidneys. In a collaborative project with Ulster University, we have been investigating microbubbles and ultrasound as a means not only of delivering but also activating drugs locally, thereby avoiding systemic toxicity. We have developed microbubbles carrying so-called sonodynamic therapy drugs that only become active when exposed to ultrasound.
A key scientific finding has been that the mechanism of activation for the drugs, may be related to the production of light by ultrasound driven bubbles (sonoluminescence). Whilst this was a well-established phenomenon in industrial ultrasonics, it was not known to be produced by microbubbles under medically relevant ultrasound conditions. Research is ongoing to further explore this finding and quantify light production.
The new microbubble formulation has been shown to be effective in multiple cancer models in vivo with negligible toxicity. It has also recently been shown to stimulate a systemic immune response and to produce a synergistic effect with an immunotherapy drug, offering the potential for a new approach to treating currently incurable metastatic disease. A spin-out company (SonoTarg Ltd) has been formed to translate the research into clinical use and a clinical trial for the treatment of pancreatic adenocarcinoma is planned.
Please see our section on blood brain barrier disruption for our work on Metastatic brain cancer.