Nasal Nanodrops Show Promise Against Aggressive Brain Tumors

Researchers at Washington University School of Medicine in St. Louis and Northwestern University have developed a groundbreaking noninvasive treatment for glioblastoma, one of the most aggressive forms of brain cancer. Their study, published on November 22, 2025, in the journal Proceedings of the National Academy of Sciences (PNAS), demonstrates how specially designed nasal nanodrops can effectively target and eliminate tumors in mice.

This innovative approach utilizes gold-core spherical nucleic acids to activate the brain’s immune response against glioblastoma tumors. By delivering these nanodrops through the nasal passages, researchers successfully avoided the need for invasive surgical procedures typically associated with current treatment options.

Understanding the Challenge of Glioblastoma

Glioblastoma is a malignant tumor that arises from brain cells known as astrocytes. This cancer type affects approximately three in every 100,000 people in the United States and is known for its rapid progression and high mortality rate. One of the primary challenges in treating glioblastoma is effectively delivering therapeutic agents to the brain.

Dr. Alexander H. Stegh, a professor and vice chair of research in the Taylor Family Department of Neurosurgery at WashU Medicine, emphasizes the importance of developing a noninvasive solution. “We wanted to change this reality and develop a treatment that activates the immune response to attack glioblastoma,” he stated. This research indicates that engineered nanostructures can safely engage immune pathways within the brain, paving the way for new methods of cancer immunotherapy.

Innovative Nanomedicine: The STING Pathway

Glioblastoma is often termed a “cold tumor,” which means it does not elicit a robust immune response. Unlike “hot tumors” that readily respond to immunotherapies, glioblastoma tends to evade immune detection. Researchers have been investigating the STING pathway (stimulator of interferon genes), which plays a crucial role in activating the immune system when foreign DNA is detected.

Prior studies have demonstrated that drugs activating the STING pathway can prepare the immune system to attack glioblastoma. However, these drugs typically degrade rapidly and require direct injection into the tumor, necessitating invasive procedures that are difficult for patients. Dr. Akanksha Mahajan, a postdoctoral research associate in Stegh’s lab and the study’s first author, noted the aim was to minimize the invasiveness associated with these treatments.

To achieve this, the research team collaborated with Dr. Chad A. Mirkin, director of the International Institute for Nanotechnology at Northwestern University, who developed the spherical nucleic acids. These nanoscale particles are densely coated with DNA or RNA and have proven to be more effective than traditional drug delivery systems.

The researchers designed a variant of these particles that contain gold nanoparticle cores and short DNA fragments, which activate the STING pathway in targeted immune cells. The nasal delivery method was chosen as it has been previously explored for brain-targeted therapies, but this is the first instance where nanoscale therapy has activated immune responses against brain tumors through this route.

Results and Future Implications

The efficacy of these nanodrops was tracked using a molecular tag that illuminated under near-infrared light, allowing the researchers to monitor the particles as they traveled from the nasal cavity to the brain. Following administration, the nanodrops activated immune responses concentrated in specific immune cells within the glioblastoma tumors. Some immune activity was also observed in nearby lymph nodes, with the therapy demonstrating minimal spread throughout the body, thereby reducing the potential for adverse side effects.

When combined with additional therapies that stimulate T lymphocytes, a vital type of immune cell, the dual treatment substantially eradicated tumors in mice and fostered long-lasting immunity against cancer recurrence. These results surpassed those achieved with existing STING-targeting therapies.

Dr. Stegh acknowledges that while the STING pathway is powerful, glioblastoma employs various strategies to undermine immune responses. His team is now investigating how to incorporate additional immune-activating features into their nanostructures, which may allow for simultaneous targeting of multiple therapeutic pathways.

“This approach offers hope for safer and more effective treatments for glioblastoma and potentially other cancers resistant to immune therapies,” Dr. Stegh remarked, highlighting a significant step towards clinical applications of this innovative treatment.

The research received funding from the National Cancer Institute of the National Institutes of Health (NIH), along with support from various cancer foundations and institutes. The authors disclosed potential conflicts of interest, with Dr. Stegh being a shareholder in Exicure Inc., and Dr. Mirkin holding shares in Flashpoint, both companies involved in developing SNA therapeutics.

In summary, this study not only represents a significant advancement in glioblastoma treatment but also opens avenues for further research into noninvasive cancer therapies.