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Targeting DIPG with Nanotechnology

A Knockout Punch for Pediatric Brain Tumors?

Targeting DIPG with Nanotechnology

by Katharine H. Hendrix

Despite decades of clinical trials to find effective therapies, the prognosis for children with diffuse intrinsic pontine glioma (DIPG), a common pediatric brain tumor, remains grim. Generally diagnosed before age ten, most DIPG patients survive less than one year. “Diffuse intrinsic pontine glioma is the worst of the worst pediatric brain tumors,” says Amy-Lee Bredlau, M.D., MSCl, a pediatric neuro-oncologist and Director of the Pediatric Brain Tumor Program at MUSC Children’s Hospital. “There is absolutely no therapy to cure DIPG. It is uniformly lethal,” she explains.

The dearth of treatment options is due in part to the location of DIPG in the pons, which rules out surgery and greatly limits the efficacy of chemotherapy.1 “The agents don’t cross the blood-brain barrier and get into the tumor tissue,” says Bredlau.

Hoping to improve the prognosis for these children, Bredlau formed a multidisciplinary team of clinicians and basic scientists focused on developing DIPG therapies. Ann-Marie Broome, Ph.D., MBA, Associate Professor in the Department of Radiology and Director of Molecular Imaging in MUSC’s Center for Biomedical Imaging, who has published widely on the design of nanoparticles for targeted therapies, most recently on the use of gold nanoparticles for that purpose,2 is one of Bredlau’s primary collaborators. Together, the group has developed new platform technologies for DIPG treatment using both organic and inorganic nanoparticles.

“We are first trying to eliminate systemic toxicity by delivering currently approved drugs where they need to be and prevent them from going where they don’t,” explains Broome. “The second problem is that tumors often develop resistance to the chemotherapy. If you don’t hit a cancer hard and fast with the correct chemotherapeutic, you run the risk of creating a new, more aggressive cancer.”

By encapsulating existing chemotherapeutic agents in organic nanoparticles such as micelles or on solid-state nanoparticles such as gold, the team can deliver higher doses directly to the tumor, with the hopes of delivering a knockout punch to the cancer.

“The doses we are delivering with these targeted therapies are a hundred times what we could give systemically. These would be fatal doses if not targeted,” adds Bredlau.

“We can target cells that will most benefit from the treatment and deliver high doses in a short window of time, which improves the likelihood that the cancer won’t be able to recover,” Broome explains.

So far, the team has produced dramatic results using targeted nanoparticles in animal models—results that were achieved much more quickly than with standard therapies (i.e., those using neither targeting nor nanoparticles). Leveraging these delivery platforms, they have increased chemotherapy doses by 10 to 1,000 fold and produced rapid tumor cell death—in some cases shortening the therapeutic window from 30 days to three.

Currently, the team has patented these platforms and is conducting in vivo studies with an eye to starting clinical trials as soon as possible.

References

1 Bredlau AL, Korones DN. Diffuse intrinsic pontine gliomas: treatments and controversies Adv Cancer Res. 2014;121:235-59.

2 Dixit S, Novak T, Miller K, Zhu Y, Kenney ME, Broome AM. Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors.Nanoscale. 2015;7(5):1782-90.

Image Above: Chemotherapy drug encapsulated in a micelle is targeted to the interior of cells. Image courtesy of Dr. Ann-Marie Broome.