To Reach a Brain Tumor, Nanoparticles Disguised Themselves as Sugar

Glioblastoma is difficult to treat not only because it grows rapidly. Most drugs penetrate the brain poorly because it is protected by the blood–brain barrier — a tightly sealed cellular filter between the bloodstream and nervous tissue.

Researchers coated lipid nanoparticles with mannose, a sugar closely related to glucose. To the protective barrier, this coating looks like legitimate cargo that can be transported through GLUT1. This transporter normally carries sugar from the blood to brain cells.

The strategy worked in two ways. First, mannose helped the particles cross the blood–brain barrier. Then they began accumulating inside the tumor itself: glioblastoma cells are particularly hungry for sugar and produce about three times more GLUT1 than normal brain tissue. The mannose-coated particles reached the brains of mice almost ten times more efficiently than uncoated particles.

The particles did not contain conventional chemotherapy. Instead, they carried messenger RNA — a temporary set of instructions for producing the protein PTEN. This protein helps restrain cell growth, but its function is often lost in glioblastoma. The delivered mRNA prompted tumor cells to produce PTEN again and restored some control over their growth.

After 28 days, tumors occupied an average of 52% of the brain in untreated animals, compared with just 2.3% in mice that received the nanoparticles. Median survival increased from 33 to 49 days. The researchers found no obvious toxic damage to the major organs.

For now, these results come from a mouse model. Further studies will be needed to assess safety and effectiveness before this therapy can be tested in patients.

Still, the approach is compelling: use the tumor’s appetite for sugar as a route for delivering a treatment that would otherwise struggle to reach the brain.