Researchers report a noninvasive nasal nanomedicine that eliminated glioblastoma in mice, tackling a major obstacle in brain cancer care: getting drugs into the brain. Glioblastoma forms from astrocytes, affects roughly three in 100,000 people in the US, progresses quickly and is almost always fatal. The new results are published in PNAS.
The team used spherical nucleic acids, precisely engineered nanostructures made by arranging short DNA strands densely around a nanoparticle core. Chad A. Mirkin, who invented spherical nucleic acids, collaborated with Alexander H. Stegh’s group at Washington University in St. Louis Medicine and Siteman Cancer Center; Akanksha Mahajan is first author. The researchers built particles with gold cores and DNA snippets designed to activate STING, the stimulator of interferon genes, an immune pathway that senses foreign DNA and triggers an immune response.
To avoid direct tumour injection, the nanomedicine was given as droplets into the nasal passages of mice. A near-infrared molecular tag showed the particles travelled along the path of the main nerve that connects facial muscles to the brain, concentrated in immune cells near and in the tumour, and did not spread widely to other body sites. The therapy activated STING and increased immune attack on tumours. When combined with drugs that help activate T lymphocytes, one or two doses eradicated tumours and produced long-term immunity, outperforming current STING treatments that require direct tumour injection. Stegh cautioned that STING activation alone is unlikely to cure glioblastoma because tumours block immune responses; his team plans to add functions to the nanostructures to activate other immune pathways and target multiple mechanisms in a single therapy, moving the work closer to clinical application.
Support came from the National Cancer Institute of the NIH, the Melanoma Research Foundation, Chicago Cancer Baseball Charities at the Lurie Cancer Center, and grants from Cellularity, Alnylam, and AbbVie. Competing interests include Stegh as a shareholder of Exicure Inc., Mirkin as a shareholder in Flashpoint, and Stegh and Mirkin as co-inventors on patent US20150031745A1.
Difficult words
- glioblastoma — A fast-growing, aggressive brain cancer from astrocytes.
- noninvasive — Not requiring cuts or entry into the body.
- nanomedicine — Medical treatment using very small engineered particles.
- spherical nucleic acid — A nanoparticle with short DNA strands densely arranged.spherical nucleic acids
- immune pathway — A series of immune reactions in the body.
- eradicate — To completely remove or destroy a disease or problem.eradicated
- immunity — The body's protection against infections or disease.
- nasal passage — The airways inside the nose used for breathing.nasal passages
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Discussion questions
- What are the main advantages and possible risks of delivering cancer treatment through the nose instead of injecting it directly into the tumour?
- The researchers say STING activation alone is unlikely to cure glioblastoma because tumours block immune responses. Why might combining multiple immune pathways improve treatment?
- If a treatment produces long-term immunity after eradicating tumours, how could that change follow-up care and monitoring for patients?
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