WASHINGTON (dpa-AFX) - Researchers at Oregon State University may have found a new way to treat glioblastoma, the deadliest type of brain cancer, with the help of tiny fat-based particles, called lipid nanoparticles, that can carry genetic material across the brain's protective barrier and directly target glioblastoma cells.
In a study published in the Journal of Controlled Release, the researchers tested the treatment in mice with glioblastoma. The nanoparticles successfully crossed the blood-brain barrier and delivered a cancer-fighting therapy, increasing the animals' median survival by 50 percent compared with untreated mice.
The nanoparticles were coated with mannose, a type of sugar that is similar to glucose, the body's main source of energy. This is important because blood vessels in the brain have a protein called GLUT1, which normally transports glucose into the brain but can also recognize mannose. The researchers used this pathway to help the nanoparticles enter the brain. Since glucose is already present in large amounts in the blood, they covered the nanoparticles with a high amount of mannose so they could better compete for the GLUT1 transporter.
'Blood contains relatively high concentrations of glucose, and that's what the nanoparticles are competing against for GLUT1's attention,' study author Oleh Taratula said. 'For the nanoparticles to get it, they need a densely coated sugar surface, and that's our central innovation. By chemically connecting mannose to cholesterol, a major structural component of the nanoparticles, we improved surface coverage sixfold.'
After crossing the blood-brain barrier, the nanoparticles collected more in tumor tissue than in healthy brain tissue as glioblastoma cells use large amounts of glucose for energy and have higher levels of the GLUT1 transporter. Inside the nanoparticles was messenger RNA (mRNA), which gives cells temporary instructions to produce proteins. In this case, the mRNA instructed cells to produce PTEN, a protein that helps stop tumor growth but is often missing in glioblastoma. Notably, restoring PTEN may help slow the growth of cancer cells. The researchers also added a special cholesterol-based ingredient to protect the mRNA until it reached the tumor.
Even though the treatments that work in animals do not always succeed in people, the researchers say their approach could help solve two major challenges in treating glioblastoma - getting medicine into the brain and delivering it directly to the tumor.
'Beyond glioblastoma, this cholesterol-based high-density functionalization strategy establishes a generalizable platform for brain-targeted mRNA therapeutics,' the authors concluded.
'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.'
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