Glioblastoma, a highly aggressive form of brain cancer, presents significant treatment challenges. Despite interventions such as surgery, radiation, and chemotherapy, survival rates remain low, with less than 30 percent of patients surviving beyond two years post-diagnosis.
Researchers are actively exploring new solutions to improve survival rates, and a team from Oregon State University has identified a promising approach: sugar-coated nanoparticles.
In a mouse study published in the Journal of Controlled Release, these sugar-coated nanoparticles have demonstrated the ability to cross the blood-brain barrier and target glioblastoma tumors directly, while avoiding significant toxicity in major organs.
The type of sugar used is crucial: mannose, which is similar to glucose. Both sugars can pass through the blood-brain barrier via the GLUT1 transporter molecule, as explained by pharmaceutical scientist Oleh Taratula: “Blood contains relatively high concentrations of glucose, and that’s what the nanoparticles are competing against for GLUT1’s attention.”
“For the nanoparticles to get it, they need a densely coated sugar surface, and that’s our central innovation.”
The breakthrough involved attaching mannose to the cholesterol forming the nanoparticles. This allowed more sugar to be packed into each nanoparticle, making them more attractive to GLUT1 and the blood-brain barrier.
During experiments with mice, sugar-coated nanoparticles reached the brain 9.9 times more efficiently than their uncoated counterparts. This is where the second advantage of mannose comes into play: glioblastoma tumors have an insatiable appetite for sugar, allowing the nanoparticles to accumulate at the tumor site, delivering mRNA instructions to produce the tumor-suppressing protein PTEN.
Drug delivery scientist Olena Taratula explains, “Glioblastoma is metabolically reprogrammed and expresses GLUT1 at three times the levels of normal brain tissue, so the particles preferentially accumulate in tumor tissue after crossing the blood-brain barrier. And restoring PTEN expression in tumor cells reinstates growth control. Across repeated dosing, tumor shrinkage occurred without any measurable organ toxicity.”
The results were promising. In untreated mice, tumors occupied an average of 52 percent of the brain after 28 days; in mice treated with the sugar-coated nanoparticles, this was reduced to just 2.3 percent. Additionally, the median survival time increased from 33 to 49 days in treated mice, indicating a significant improvement, although not a cure.
While these findings are limited to mice, they represent a promising step forward. The sugar coating effectively addresses two challenges, and further studies are needed to determine how this approach might translate to human glioblastoma treatment.
Researchers are making strides in glioblastoma treatments, ranging from nasal drops that block tumor growth to methods that enhance immune responses. The sugar-coated nanoparticle strategy could potentially be applied beyond brain cancers, enabling precise delivery of therapies across the blood-brain barrier.
Related: The ‘Breaking Bad’ Effect From Cancer Is Real, Study Finds
The researchers note in their paper, “Beyond glioblastoma, this cholesterol-based high-density functionalization strategy establishes a generalizable platform for brain-targeted mRNA therapeutics. These findings establish mannose-cholesterol lipid nanoparticles as a promising translational platform for mRNA-based therapy of glioblastoma and potentially other neurological disorders requiring therapeutic intervention in the brain.”
The research has been published in the Journal of Controlled Release.
This article was fact-checked by Clare Watson and edited by Rebecca Dyer. While we pride ourselves on our process, we are only human. If you spot a mistake, please let us know.
