Nasal Nanodrops Show Promise Against Glioblastoma in Mice

Researchers at Washington University School of Medicine in St. Louis, in collaboration with scientists from Northwestern University, have developed a groundbreaking treatment for glioblastoma, one of the most aggressive forms of brain cancer. This new technique utilizes nanodrops delivered nasally to activate the brain’s immune response, effectively targeting and eliminating tumors in mice. The findings could pave the way for noninvasive therapies that transform brain cancer treatment.

The study, published in the Proceedings of the National Academy of Sciences (PNAS) in November 2025, highlights a novel approach to treating glioblastoma through the activation of the STING immune pathway. By employing gold-core spherical nucleic acids, the researchers were able to deliver potent cancer-fighting compounds directly to the brain without the need for invasive surgical procedures.

Challenges in Treating Glioblastoma

Glioblastoma arises from astrocytes, a type of brain cell, and is the most common malignant brain tumor, affecting approximately three in every 100,000 individuals in the United States. The rapid progression of this disease and its typically fatal prognosis present significant hurdles for treatment, chiefly the difficulty of delivering effective therapies to the brain.

Dr. Alexander H. Stegh, a professor and vice chair of research in the Taylor Family Department of Neurosurgery at WashU Medicine, expressed the urgency of finding noninvasive treatment methods. “We wanted to change this reality and develop a noninvasive treatment that activates the immune response to attack glioblastoma,” Stegh said. This research has demonstrated that precisely engineered nanostructures can activate powerful immune pathways within the brain, redefining possibilities for cancer immunotherapy.

Innovative Nanotherapy with STING Activation

Glioblastoma is often referred to as a “cold tumor” because it typically fails to provoke a robust immune response. Unlike “hot tumors,” which respond better to immunotherapy, glioblastomas can evade detection by the immune system. To address this, the researchers focused on the STING pathway, which is activated when cells detect foreign DNA. Previous studies indicated that drugs activating this pathway could prime the immune system against glioblastoma, but these drugs often degrade quickly and require invasive delivery methods.

Dr. Akanksha Mahajan, a postdoctoral research associate in Stegh’s lab and the study’s first author, noted the team’s desire to minimize patient discomfort. “We thought that we could use the spherical nucleic acid platforms to deliver these drugs in a noninvasive way,” she stated.

To enhance the delivery of these therapeutics, the research team collaborated with Dr. Chad A. Mirkin, a leading figure in nanotechnology at Northwestern University. Mirkin’s development of spherical nucleic acids, densely coated with DNA or RNA, proved to be a crucial component of their treatment strategy. The researchers created a specialized version featuring gold nanoparticle cores that activate the STING pathway in targeted immune cells, utilizing the nasal passages for delivery.

The innovative approach demonstrated for the first time that nanoscale therapeutics could activate immune responses against brain tumors through nasal delivery, a promising advancement in the field.

Results and Future Implications

The study’s researchers tracked the movement of the nanodrops to verify selective delivery to the brain and activation of target immune cells. By incorporating a molecular tag that fluoresces under near-infrared light, they observed the nanodrops traveling along the facial nerve pathway to the brain. Upon reaching their destination, the immune response triggered by the nanomedicine concentrated within specific immune cells in the tumor, with some activity also observed in nearby lymph nodes. Importantly, the therapy showed limited systemic spread, reducing the risk of potential side effects.

When combined with treatments that enhance T lymphocyte activity, a critical immune cell type, the two-dose regimen not only eradicated tumors in mice but also fostered long-lasting immunity, preventing cancer recurrence. These results significantly outperformed existing STING-targeting therapies.

Dr. Stegh emphasized that while stimulating the STING pathway is not a standalone solution for glioblastoma, the study represents a vital step towards developing more effective and safer treatments. He mentioned that glioblastoma employs various strategies to undermine immune responses, and his team is exploring ways to incorporate additional immune-activating features into their nanostructures.

“This approach offers hope for safer, more effective treatments for glioblastoma and potentially other immune treatment-resistant cancers, marking a critical step toward clinical application,” Stegh concluded.

The research received support from the National Cancer Institute of the National Institutes of Health, among other organizations. The potential of this innovative treatment strategy could lead to significant advancements in the fight against one of the most challenging cancers, opening doors for further exploration and clinical testing.