gene therapy

To treat brain cancer, just add water

JOHNS HOPKINS (US) — Freeze-dried nanoparticles can deliver gene therapy into human brain cancer cells—and may one day offer an alternative to brain surgery.

The freeze-dried particles, which can be stored for up to three months prior to use, may rule out the need for virus-mediated gene therapy, which has safety concerns. The new findings are reported in the journal Biomaterials.

“Most nonviral gene therapy methods have very low efficacy,” says Jordan Green, assistant professor of biomedical engineering at Johns Hopkins University.

Nanoparticles are particles that have at least one dimension 100 billionths of a meter or less in length.

To develop the gene therapy nanoparticle, researchers started with store-bought small molecules and systematically mixed combinations together to generate chemical reactions that resulted in different polymers.

They then mixed DNA that encodes a glowing protein with each different polymer to allow it to bind to the polymers and form nanoparticles.

Each sample was added to human brain tumor cells and human brain tumor stem cells. After 48 hours, the team counted how many cells had taken up the nanoparticles and were making the glowing protein encoded by the introduced DNA.

Success was rated by counting how many cells survived and what percentage of those cells glowed.

Of the combinations tested, one particular formulation of so-called poly (beta-amino ester) nanoparticles did particularly well at getting into both glioblastoma and brain tumor stem cells.

The nanoparticles were then freeze-dried and stored at different temperatures (freezer, refrigerator, and room temperature) for different lengths of time, and were then retested for their ability to get into cells.

After six months in storage, the effectiveness dropped by about half, but the team found that at up to three months of storage at room temperature, there was virtually no change in effectiveness. Certain nanoparticles even had a particular affinity for brain tumor cells over healthy brain cells.

“I could imagine particles based on this technology being used in conjunction with, and even instead of brain surgery,” says Alfredo Quinones-Hinojosa, associate professor of neurosurgery and oncology at Johns Hopkins.

“I envision that one day, as we understand the etiology and progression of brain cancer, we will be able to use these nanoparticles even before doing surgery—how nice would that be?  Imagine avoiding brain surgery altogether.”

The study was funded by the Institute for NanoBioTechnology at The Johns Hopkins University, the Maryland Stem Cell Research Fund, the National Institutes of Health, the Howard Hughes Medical Institute and the Robert Wood Johnson Foundation.

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