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Researchers at Washington University School of Medicine and Northwestern University have developed an intranasal nanodrop that delivers an immune-boosting drug to the brain, showing promising results against glioblastoma in mice. This approach uses engineered nanoscale structures to activate a brain immune pathway while avoiding systemic side effects.
Nanoengineered droplets and the STING switch
The treatment is built around spherical nucleic acids (SNAs): tiny gold-core nanoparticles wrapped in short DNA strands. These SNAs are designed to activate the STING (Stimulator of Interferon Genes) pathway inside immune cells. Activating STING ramps up a local immune response that can help the brain recognize and attack tumor cells—critical for so-called "cold" tumors like glioblastoma that typically evade immune detection.
Why STING matters in glioblastoma therapy
Glioblastoma originates from astrocytes and is one of the most aggressive and lethal brain cancers. Traditional immunotherapies often fail because glioblastoma actively suppresses immune activation in the tumor microenvironment. By turning on STING in immune cells near the tumor, researchers aim to convert a cold tumor into a more inflamed, treatment-responsive state.
Intranasal delivery: a direct route to the brain
One of the key innovations is the delivery pathway. Instead of systemic injection, the researchers applied the nanodrops intranasally. Imaging and tissue analysis indicate the nanoparticles travel along cranial nerve routes—the primary branch of the facial nerve—into the brain and concentrate around tumor-associated immune cells. This targeted delivery minimizes transfer to other organs and lowers the risk of off-target immune activation or systemic toxicity.
In mouse models, a single or just a couple of doses of the intranasal SNAs that activate STING, combined with drugs that enhance T cell activity, cleared tumors and produced durable anti-tumor immunity. Importantly, the therapy activated immune cells specifically in the tumor area rather than triggering a broad, body-wide immune response.
From lab bench to clinical hope: implications and next steps
Alexander H. Steg, professor and vice chair for research in the Department of Neurosurgery at Washington University, described the project as an effort to create a noninvasive way to engage the brain's immune defenses against glioblastoma. While the results in animals are encouraging, Steg and colleagues caution that STING activation alone is unlikely to be a complete cure because glioblastoma uses multiple mechanisms to suppress immunity. The team is now working to augment the SNAs so they can trigger several immune pathways simultaneously.
The work, published in PNAS, suggests a pathway for safer, more focused immunotherapy for brain cancers that are currently hard to treat. Beyond glioblastoma, intranasal nanodelivery could be adapted to other neurologic tumors or disorders where localized immune modulation is desirable.
Next challenges and technological prospects
- Translational hurdles: scaling nanoparticle manufacturing, ensuring safety in larger animals and humans, and meeting regulatory requirements.
- Combination strategies: pairing STING-activating nanodrops with checkpoint inhibitors, T cell boosters, or targeted radiation to overcome tumor immunosuppression.
- Targeting precision: refining nasal-to-brain delivery routes to hit diverse tumor locations without affecting healthy tissue.
Imagine a future where a noninvasive nasal spray helps the immune system see and eliminate brain tumors—this study marks an important step toward that possibility, though careful clinical development lies ahead.
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