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Nanotech Treatment Studied for Brain Tumors

Glioblastoma cells in culture

Glioblastoma cells in culture (Wellcome Images, National Cancer Institute)

13 July 2017. Medical researchers and engineers designed and tested in mice a way to deliver gene-silencing therapies in nanoscale particles to treat glioblastoma, an aggressive form of brain cancer. Results of the study by a team from Northwestern University and Massachusetts Institute of Technology appear in the 10 July issue of Proceedings of the National Academy of Sciences (paid subscription required).

Glioblastoma is a cancer that forms in the brain’s glial cells that support the functioning of neurons in the brain sending and receiving nerve signals. The cancer generally grows and spreads quickly, often resulting death within 15 months of diagnosis. The genetic make-up of glioblastoma can also vary from one person to the next, making it more difficult to find treatments. American Association of Neurological Surgeons estimates glioblastoma, also known as glioblastoma multiforme, occurs in 2 to 3 out of 100,000 adults per year, and accounts for 52 percent of all primary brain tumors.

Researchers led by Northwestern neurosurgeon and cancer specialist Maciej Lesniak are seeking more effective treatments for glioblastoma, for which there are few. A promising target for glioblastoma therapies are brain tumor-initiating cells, or BTICs, that help drive the cancer’s aggressiveness. BTICs are responsible for the rapid spread of the disease, as well as its resistance to conventional treatments and recurrence.

But BTICs are also elusive and difficult to target, since they can arise from a number of genetic sources and can adapt to various conditions in the brain. Other researchers discovered that successfully attacking BTICs requires simultaneously stopping 4 transcription factors, proteins for converting the genetic codes in DNA to ribonucleic acid or RNA instructions for producing proteins used by cells. The strategy devised by Lesniak and colleagues is designed to block the effects of these key transcription factors, and thus stop BTICs.

The team’s treatments use small interfering RNAs, pieces of RNA that, as the name implies, interfere with production of the chemical signals to produce proteins for cells. In this case, the small interfering RNAs are designed to stop the 4 transcription factors that make BTICs, in effect silencing the mutated genes responsible for producing BTICs. The small interfering RNAs can also be adjusted to reflect the precise mutations expressed in the patient.

To deliver the small interfering RNAs, the Northwestern researchers adapted a process developed at MIT in the chemical engineering labs of Robert Langer and Daniel Anderson, co-authors of this study. That delivery process packages the small interfering RNAs in nanoscale polymer capsules made from natural biocompatible oils. The nanoscale particles — 1 nanometer equals 1 billionth of a meter — are then injected into the tumors.

The researchers tested the gene-silencing nanoparticles in lab cultures and mice grafted with human glioblastoma tumors driven by BTICs. In both cases, the gene-silencing nanoparticles stopped the growth of tumor cells, and extended the survival times of mice grafted with human brain tumors.

“Nanomedicine provides a unique opportunity to advance a therapeutic strategy for a disease without a cure,” says Lesniak in a Northwestern University statement. The team next plans to refine the process and test further for long-term effects. Langer and Anderson filed for a patent on its polymer nanoparticle delivery technique.

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