Research Grant - 2023

Project Summary:

Approximately 1900 individuals in Australia receive a diagnosis of brain cancer each year, sadly resulting in around 1500 annual fatalities from this relentless disease. Despite substantial advancements in therapies designed to combat glioblastoma multiforme (GBM), it remains a daunting challenge, characterised by a grim prognosis and no permanent cure. Temozolomide (TMZ) stands out as the only orally available FDA approved chemotherapy for GBM treatment. However, it grapples with challenges, including inadequate oral bioavailability, limited tumour penetration (below 20%), and susceptibility to resistance. While other therapeutic options, such as intravenous administration of targeted therapies like Bevacizumab, may come into play when glioblastoma recurs or fails to respond to alternative treatments, they, too, fall short of delivering curative or long-lasting effects. This underscores the urgent need for the development of innovative treatment approaches, particularly those that enhance the efficient delivery of established chemotherapeutic drugs like TMZ.

Hence, our primary objective revolves around encapsulating TMZ within biodegradable, clinically applicable smart nanoparticles. This pioneering approach holds promise in safeguarding TMZ within the bloodstream, enhancing its bioavailability, and augmenting its ability to infiltrate tumour cells through active targeting mechanisms. We firmly believe that our strategy will significantly elevate TMZ’s bioavailability within tumours through a multi-modal approach. Our strategy holds the promise of reducing the effective dosage and dosing frequency of TMZ, which, in turn, has the potential to mitigate or delay drug resistance while simultaneously improving the clinical outcomes and overall quality of life for GBM patients.

Reports:

In July 2025, results related to this research grant were published in the Journal of Nanobiotechnology. Summary of key findings:

• Researchers created silica-based nanoparticles coated with polyethyleneimine (PEI) to deliver therapeutic RNA molecules into brain tumor cells.
• By carefully adjusting the PEI coating, they reduced toxicity while keeping the particles effective at carrying the RNA.
• These nanoparticles carried molecules that block harmful RNAs (miR-21 and miR-210), leading to good uptake by brain tumor cells and even reaching deep areas of 3D tumor models.
• In lab tests, the treatment shrank tumor-like structures by about 30% and reduced cancer cell colonies by about 40%, while also showing the ability to cross a model of the blood-brain barrier.

The full article is open access, and can be accessed here >