Researchers at Washington University School of Medicine in St. Louis, working with researchers at Northwestern University. They have devised a noninvasive treatment for one of the most aggressive and lethal brain malignancies. Their approach uses carefully nano-medicine to deliver effective tumor-fighting therapy to the brain via nasal drops. The innovative delivery approach is less intrusive than similar treatments in development.
The findings were published this month in the journal PNAS.
Glioblastoma tumors develop from brain cells known as astrocytes. And are the most prevalent type of brain cancer, affecting approximately three in 100,000 people in the United States. Glioblastoma typically advances swiftly and is virtually always deadly. There are no curative treatments for the condition, in part because getting drugs to the brain is extremely difficult.
Cold tumors warmed up with STING
Glioblastoma tumors referred as “cold tumors” because they do not elicit the body’s natural immune response. As opposed to “hot tumors,” which are more easily treated with immunotherapies. Researchers have devised methods to elicit an immune response to cancers by activating a system within cells known as STING. That stands for ‘stimulator of interferon genes’. STING occurs when a cell identifies foreign DNA and stimulates the immune system to combat the threat.
Previous research has indicated that medicines that activate STING in glioblastoma tumors help prime the immune system. To better combat the malignancy. However, these medicines degrade quickly in the body and directly administers to the tumor in order to function. Because frequent dose is required for long-term effectiveness, using direct intratumoral injection necessitates extremely invasive procedures.
To address the problem, the Stegh team collaborated with Chad A. Mirkin, a prominent figure in nanotechnology at Northwestern University. Mirkin’s invention of spherical nucleic acids, which densely arrange DNA or RNA around a nanoparticle core, has proven to be more effective therapeutically than conventional methods. The researchers developed a new class of these structures, featuring gold cores with DNA snippets to activate the STING pathway in selected immune cells. For brain delivery of these drugs, the team utilized the nasal route.
The team demonstrated that a specific approach could selectively deliver medicine to the brain and act on targeted cells. Using a molecular tag visible under near-infrared light, they showed that the nanomedicine, administered as droplets into the nasal passages of glioblastoma-infected mice, traveled along the nerve pathway to the brain. The immune response was concentrated in the tumor’s specific immune cells, triggering beneficial responses in the lymph nodes without unwanted spread to other body parts. Additionally, the therapy effectively activated the STING pathway, bolstering the immune system’s fight against the tumor.
Combining the new therapy with T lymphocyte-activating drugs effectively eliminated tumors with one or two doses and provided long-term immunity against recurrence, significantly outperforming existing STING-activating immune therapies.
Stegh Said:
“This is an approach that offers hope for safer, more effective treatments for glioblastoma and potentially other immune treatment-resistant cancers, and it marks a critical step toward clinical application,
