‘guided missile’ a key for brain cancer
Press Release | May 13, 2020

RESEARCHERS have developed a brain cancer drug that can cut through the brain’s protective coating in a major breakthrough that could save thousands of lives.

Glioblastoma has the worst survival rate of all cancers, with only 4% of patients surviving five years past their diagnosis.  Little has been achieved to improve this survival rate in the past 30 years, and one major reason is the difficulty in successfully getting chemo- or radiotherapeutics into the brain, making surgery the most reliable treatment method. Unfortunately, most patients that undergo surgical resection of glioblastoma have a relapse within six to twelve months after the removal of the tumour with a more aggressive and treatment-resistant form of the cancer. The need to deliver more potent and targeted therapeutics to brain tumours will offer a significant increase in survival, but new delivery tools are needed. While the skull protects against physical damage, the coating, known as the blood-brain barrier, provides a defence against disease-causing pathogens and toxins present in our blood. Unfortunately, it also blocks medicines entering the brain.

But a new delivery method for brain cancer treatment that worked in mice and human clinical trials could begin at the end of this year. CBNS researcher CI Professor Kris Thurechts, also from UQ’s Centre for Advanced Imaging (CAI) and the Australian Institute for Bioengineering and Nanotechnology (AIBN), said the nanomedicine his team developed not only got into the tumour tissue but also travelled to the core of the tumour. “The blood-brain barrier is exquisite until you need to treat something in the brain”.

A synthetic nanoparticle called polyethylene glycol, or PEG, is wrapped around a small dose of the medicine doctors wish to use. The PEG acts like a lolly wrapper making the medicine invisible to the immune system, allowing it to cross the blood-brain barrier. Once in the brain tumour, the high acid levels in cancer cells trigger the release of the drug from its wrapper.

The collaborative research, published in the American Chemical Society journal Central Science, with Dr Zach Houston as first author, showed the nanoparticles pierced the blood-brain barrier in mice who had a common brain cancer called glioblastoma. The drug then went to work destroying the tumour cells while leaving healthy cells untouched. “Nanomedicines have been called guided missiles,” Professor Thurecht said.

Nanomedicines are therapeutic delivery shuttles that are 100s of time larger than the therapeutic payload and have been investigated for their potential to treat cancer more effectively. Their hallmark advantages are increased payload delivery through longer circulation, low recognition and premature clearing by the immune system, and significantly reduced to non-existent side-effects. Despite these distinct advantages, nanomedicines were previously thought to have not much place in the treatment of brain cancer, as their size and chemical properties are not congruent with molecules known to enter the brain efficiently.

Paper: Understanding the Uptake of Nanomedicines at Different Stages of Brain Cancer Using a Modular Nanocarrier Platform and Precision Bispecific Antibodies

News article: New Cancer drug works like a guided missile. Herald Sun by Sue Dunlevy. 13th May 2020

Image of Dr Houston and Professor Thurecht by UQ Centre for Advanced Imaging.