Revolutionary Nasal Nanodrops Target Brain Tumors in Mice

Research teams at Washington University School of Medicine in St. Louis and Northwestern University have developed innovative nasal-delivered nanodrops that show significant promise in treating aggressive glioblastoma tumors in mice. This groundbreaking method leverages gold-core spherical nucleic acids to activate the immune system’s STING pathway, providing a noninvasive treatment option that could redefine brain cancer therapy.

The findings, published on November 22, 2025, in the journal PNAS, highlight a vital advancement in the ongoing battle against glioblastoma, a cancer notorious for its rapid progression and poor prognosis. Current treatment options remain largely ineffective due to the difficulty of delivering effective therapies directly to the brain.

Alexander H. Stegh, PhD, a prominent researcher and vice chair of the Taylor Family Department of Neurosurgery at Washington University, emphasized the significance of this research. “We wanted to change this reality and develop a noninvasive treatment that activates the immune response to attack glioblastoma,” he stated. Stegh also directs research at The Brain Tumor Center at the Siteman Cancer Center.

Glioblastoma arises from astrocytes, a type of brain cell, and is the most common malignant brain tumor, affecting approximately three in every 100,000 people in the United States. The tumor’s ability to evade immune detection has made it particularly challenging to treat effectively.

Innovative Approach to Immune Activation

The novel approach employs carefully engineered nanostructures designed to deliver potent cancer-fighting compounds directly to the brain via nasal drops. This technique avoids the invasive procedures often associated with current treatments.

The research team, led by Akanksha Mahajan, PhD, a postdoctoral associate in Stegh’s lab, focused on the STING pathway, which triggers immune defenses upon the detection of foreign DNA. Previous methods required direct injection into tumors, making them both invasive and impractical for repeated use.

“Using spherical nucleic acid platforms, we can deliver these drugs in a noninvasive way,” Mahajan explained. The team partnered with Chad A. Mirkin, PhD, who pioneered the development of spherical nucleic acids, small particles densely coated with DNA or RNA capable of more effective delivery of therapeutic agents.

To achieve this, researchers created specialized spherical nucleic acids featuring gold nanoparticle cores that activate the STING pathway in specific immune cells. By utilizing the nasal passages as an entry point, they aimed to demonstrate an effective method of delivering nanomedicine to the brain.

Successful Trials and Long-Lasting Immunity

In laboratory tests involving mice with glioblastoma, the nanodrops successfully traveled through the facial nerve pathways to the brain. The tagged nanodrops glowed under near-infrared light, allowing researchers to track their movement and confirm that immune cell activation occurred within the tumor. The therapy demonstrated minimal spread throughout the body, significantly reducing the likelihood of adverse side effects.

When combined with additional drugs that enhance T-cell activity, the dual treatment not only eliminated tumors in mice but also fostered long-lasting immunity against cancer recurrence. Stegh remarked that while stimulating the STING pathway is a vital step, glioblastoma’s complex defenses necessitate further enhancements to their nanostructures to bolster immune activation.

“This approach offers hope for safer, more effective treatments for glioblastoma and potentially other cancers resistant to immune therapies,” he noted, highlighting that this research marks a crucial step toward clinical applications.

The study received funding from the National Cancer Institute of the NIH and several other institutions. It represents a significant leap forward in addressing one of the most challenging cancers, with the potential to reshape future therapies.

As researchers continue to refine this technology, there is optimism that these breakthroughs could ultimately lead to more effective treatment options for patients facing aggressive brain cancers.