Biodegradable nanoparticle can deliver 'suicide gene' to pediatric brain tumor cells in mice

Biodegradable nanoparticle can deliver 'suicide gene' to pediatric brain tumor cells in mice

Johns Hopkins researchers report that a type of biodegradable, lab-engineered nanoparticle they fashioned can successfully deliver a "suicide gene" to pediatric brain tumor cells implanted in the brains of mice. The poly(beta-amino ester) nanoparticles, known as PBAEs, were part of a treatment that also used a drug to kill the cells and prolong the test animals' survival. In their study, described in a report published January 2020 in the journal Nanomedicine: Nanotechnology, Biology and Medicine , the researchers caution that for safety and biological reasons, it is unlikely that the suicide gene herpes simplex virus type I thymidine kinase (HSVtk) -- which makes tumor cells more sensitive to the lethal effects of the anti-viral drug ganciclovir -- could be the exact therapy used to treat human medulloblastoma and atypical teratoid/rhabdoid tumors (AT/RT) in children. So-called "suicide genes" have been studied and used in cancer treatments for more than 25 years. The HSVtk gene makes an enzyme that helps restore the function of natural tumor suppression. Specifically, the experiments found that a combination of the suicide gene and ganciclovir delivered by intraperitoneal injection to mice killed more than 65% of the two types of pediatric brain tumor cells. The combination was deliberately "transfected" with the gene seven days after the nanoparticle therapy was used to deliver the genetic material. Mice bearing an AT/RT-type tumor lived 20% longer after receiving the treatment -- 42 days, compared to 35 days for untreated mice. Those with a group 3 medulloblastoma-type tumor implanted in the brain lived 63% longer, surviving 31 days compared to 19 days for untreated mice. It's an exciting alternate way to be able to deliver gene therapy to a tumor in a selective fashion that targets only tumor cells. Our idea now is to find other collaborators who may have a gene therapy that they think would work well to kill these tumors." Eric Jackson, M.D., associate professor of neurosurgery at the Johns Hopkins University School of Medicine Medulloblastoma and AT/RT are two of the most prevalent and deadly pediatric brain malignancies. Traditional treatments, including radiation, can harm healthy tissue as well as the tumor, and can produce long-lasting developmental side effects in growing children, making it critical to find new therapies, Jackson notes. Gene therapy that targets only cancer cells is a promising treatment avenue, but many gene therapy methods use a modified virus to deliver their therapeutic payloads of DNA, a method that may not be safe or suitable for pediatric use. "A lot of these viruses are safe if you have a mature immune system, but in very young patients with more fragile immune systems, a virus delivery system may pose additional risks," says Jackson. Related Stories



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