Nasal Drops Carry Immunotherapy Into the Brain, Slowing Deadly Glioblastoma in Mice

Researchers have engineered nasal drops that travel along olfactory nerves into the central nervous system to deliver immunotherapy against glioblastoma, an aggressive and often fatal brain tumor.

Early tests in mice show the treatment reached its target safely and activated immune pathways that slowed tumor growth. The team packaged STING‑activating genetic material as spherical nucleic acids wrapped around tiny gold nanoparticle cores to improve stability and delivery to the brain.

'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,' said neurosurgeon Alexander Stegh of Washington University.

Glioblastomas are highly aggressive, evade early detection, and blunt the body's normal immune responses, making them difficult to treat. They also form within the sensitive central nervous system, where surgical access and conventional drug delivery are especially challenging.

Previous work showed that activating interferon response genes via the STING pathway can alert the immune system to tumors, but STING‑triggering drugs typically break down rapidly and have required repeated, invasive administration to reach brain tumors.

To overcome that limitation, neuroscientist Akanksha Mahajan and colleagues converted STING‑activating molecules into spherical nucleic acids and wrapped them around a gold nanoparticle core. This design preserves activity longer and enables noninvasive delivery through the nose.

In mice bearing glioblastomas, the gold‑backed spherical nucleic acids activated the STING pathway in the brain and suppressed tumor growth. The researchers caution that cancer cells can bypass a single immune pathway, so the approach will likely need combination therapies.

Importantly, when the nasal drops were paired with additional immune‑boosting drugs, the animals developed durable, long‑term immunity to glioblastoma in these experiments.

'With this research, we've shown that precisely engineered nanostructures, called spherical nucleic acids, can safely and effectively activate powerful immune pathways within the brain,' Stegh said.

The study appears in the Proceedings of the National Academy of Sciences (PNAS). While results in mice are promising, authors emphasize that human clinical trials are still required to determine safety and effectiveness in people.

Context: Glioblastoma is the most common malignant brain tumor and has a very poor prognosis; only about 6.9% of patients survive beyond five years after diagnosis. The researchers note this nasal delivery strategy could reduce the need for repeated invasive procedures if translated successfully to humans.