China-US team creates nano-plant drug for deadliest brain cancer

September 09, 2024

A new plant-based nanoparticle treatment for glioblastoma, the fastest growing and most aggressive form of brain cancer, has been developed by scientists in China and the US.

Researchers from Renmin Hospital of Wuhan University and Yale University found that bardoxolone methyl (BM) – a phytochemical capable of self-assembly into spindle-shaped nanoparticles – was able to effectively target tumour cells when injected into mice.“These nanoparticles are designed to overcome the dual challenges of effectively killing [glioblastoma] cells and efficiently penetrating the brain,” the team said in a paper published in the August issue of the peer-reviewed journal, Small Science.

These spindle-shaped nanoparticles have a diameter of just 50 to 80 nanometres and a length of around 170 nanometres. A nanometre is one-millionth of a millimetre – an average sheet of paper has of thickness of around 100,000 nanometres.Nanomedicine is an area that is showing a lot of potential in the fight against cancer. And the BM nanoparticles are displaying a lot of promise as a safe treatment for glioblastoma in particular.

Glioblastoma is one of the most common forms of cancer that originates in the brain or spinal cord. It is also one of the most aggressive: those diagnosed with it are immediately classified as stage four, the most advanced cancer stage.Globally, around 250,000 people are diagnosed with glioblastoma every year. After diagnosis, the median survival time is just 14 to 16 months.

Currently, treatment includes surgery to remove the tumour followed by radiation and chemotherapy. But this type of cancer resists conventional therapies, so the treatment can have little effect on the disease.A reason for this is the lack of drugs that can cross the blood-brain barrier, a membrane that protects the brain from pathogens and toxins.It is a challenge the research team has been trying to address.They said they recently discovered a group of phytochemicals derived from medicinal plants that were able to self-assemble into nanoparticles to treat various diseases.

Among these phytochemical nanoparticles, which are able to enhance the permeability of the blood-brain barrier, BM was found to be “highly effective” in killing glioblastoma cells.Potential carcinogens in almost 90% of instant noodles tested, Hong Kong consumer watchdog findsWhen the BM nanoparticles were also combined with the anticancer peptide P28 and vasodilator lexiscan (LEX), the resulting P28-LBM nanoparticles were found to even better penetrate the tumours.

This is due to an autocatalytic effect – when the nanoparticle reaches the tumour, the release of LEX makes the membrane more permeable, which in turn allows in more nanoparticles.The team found that the BM nanoparticles killed the tumour cells by inducing a type of cell death called pyroptosis, as well as inhibiting the epithelial-mesenchymal transition – a process which is involved in tumour progression.

Injecting the P28-LBM nanoparticles into the tail veins of mice three times a week for four weeks led to “pronounced suppression of tumour growth”.“Notably, no significant weight loss was observed in the mice, indicating minimal systemic toxicity, and suggesting potential safety for intravenous administration,” the team wrote, adding that no obvious tissue damage or liver toxicity was observed either.The team said the spindle shape of the nanoparticles might allow for enhanced cellular uptake and tumour penetration compared to spherical particles.“The P28-LBM nanoparticles present a promising approach for [glioblastoma] treatment, with potential for effective and safe clinical applications in the future,” they wrote.