A novel nasal-delivered nanotherapy has shown promise against glioblastomas in mice. The corresponding study was published in the Proceedings of the National Academy of Sciences.
"This is the first time that it has been shown that we can increase immune cell activation in glioblastoma tumors when we deliver nanoscale therapeutics from the nose to the brain," said first author of the study, Akanksha Mahajan, PhD, a postdoctoral research associate at the Washington University School of Medicine, in a press release.
Unlike ‘hot tumors’, which tend to be more responsive to immunotherapies, glioblastomas- often called 'cold tumors'- tend to evade detection. Previous research, however, shows that drugs that activate a pathway known as ‘stimulator of interferon genes’ or ‘STING’ can prime the immune system to attack glioblastomas.
A downside of these drugs, however, has been that they degrade quickly and must be directly injected into the tumor multiple times. To overcome this hurdle, the researchers behind the current study engineered a specialized version of spherical nucleic acids with gold nanoparticle cores and short DNA fragments that trigger the STING pathway in targeted immune cells. They chose to deliver the particles intranasally.
The system was tested out on mice with glioblastomas, triggering an immune response concentrated in specific immune cells within the tumors. Further examination revealed that immune cells in and around the tumors activated the STING pathway. Coupling the nanotherapy with drugs that help activate T lymphocytes was found to eliminate tumors in the mice and trigger long-lasting immunity preventing relapse.
"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 co-corresponding author of the study, Alexander H. Stegh, PhD, a professor at the Washington University School of Medicine, in a press release.
"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. This redefines how cancer immunotherapy can be achieved in otherwise difficult-to-access tumors,” he concluded.
Sources: Science Daily, Proceedings of the National Academy of Sciences
