Scientists at Oregon State University have developed a new experimental treatment that could one day improve care for people with glioblastoma, the most aggressive and deadly form of brain cancer.
The research offers hope because this cancer is extremely difficult to treat, and most patients survive only a short time after diagnosis.
Glioblastoma grows quickly and spreads into nearby brain tissue, making it hard for surgeons to remove every cancer cell.
Even after surgery, patients usually need radiation therapy and chemotherapy, but the tumor often returns. New treatments are urgently needed because fewer than one-third of patients are alive two years after diagnosis.
The study was led by Oleh Taratula, Olena Taratula, and Yoon Tae Goo from the Oregon State University College of Pharmacy. Their findings were published in the Journal of Controlled Release.
One of the biggest challenges in treating brain cancer is the blood-brain barrier. This natural barrier protects the brain by blocking many harmful substances in the blood, but it also prevents many medicines from reaching brain tumors.
Even when drugs enter the brain, they may not reach enough cancer cells without also affecting healthy tissue.
To solve this problem, the researchers designed tiny fat-based particles known as lipid nanoparticles. These particles carried messenger RNA, or mRNA, containing instructions for cells to make a protein called PTEN. PTEN normally helps stop cells from growing out of control, but it is often missing or inactive in glioblastoma.
The team then coated the nanoparticles with mannose, a natural sugar that closely resembles glucose. Brain cells have a transport system called GLUT1 that normally moves glucose into the brain for energy. Because GLUT1 also recognizes mannose, the sugar coating helped the nanoparticles cross the blood-brain barrier.
The researchers further improved the design by attaching mannose to cholesterol, allowing much more sugar to cover each particle. This helped the nanoparticles compete with glucose for access to GLUT1 and increased the amount that entered the brain.
Glioblastoma cells produce much higher levels of GLUT1 than normal brain cells. After entering the brain, the nanoparticles naturally collected inside the tumors, where the mRNA restored PTEN production. In mouse experiments, repeated treatment shrank tumors without causing measurable damage to major organs.
The results were encouraging. Mice receiving the treatment lived about 50% longer than untreated mice. Although studies in animals do not guarantee the same results in humans, they are an important first step before clinical trials can begin.
Review and analysis: This study combines two modern technologies—mRNA therapy and targeted nanoparticles—to overcome one of the biggest barriers in brain cancer treatment.
The findings are promising because the treatment both crossed the blood-brain barrier and selectively targeted tumor cells. However, the work is still in mice, and extensive safety testing and human clinical trials will be needed before it could become an approved treatment.
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Source: Oregon State University.
