Focused Ultrasound Facilitates Delivery of Intranasal Nanoparticles to the Brain


Dr. Hong Chen’s group at Washington University in St. Louis (WUSTL) recently announced results from their collaborative work with colleagues in pediatrics, radiology, and aerosol chemistry to deliver gold nanoclusters to the brain and then enhance their local delivery with focused ultrasound. An Assistant Professor of Biomedical Engineering, Chen carried out this work together with faculty from the Department of Pediatrics at the School of Medicine, the Mallinckrodt Institute of Radiology, and the Department of Energy, Environmental, & Chemical Engineering in the School of Engineering & Applied Science. Their collaborative manuscript, “Focused ultrasound combined with microbubble-mediated intranasal delivery of gold nanoclusters to the brain,” was recently published in the Journal of Controlled Release.

The group is especially interested in translating this technique into a treatment for difficult and rare childhood brain cancers, such as diffuse intrinsic pontine gliomas (DIPG). The team calls their focused ultrasound with intranasal delivery technique “FUSIN,” and the intranasal delivery allows the olfactory and trigeminal nerves to carry the nanoparticles directly to the brain, bypassing the blood-brain barrier. The concept of FUSIN was initially proposed in a 2014 publication in PlosOne by Chen and her former postdoctoral adviser, Dr. Elisa Konofagou, as well as other coauthors.

“At the beginning, I couldn’t even believe intranasal delivery could work,” said Chen. “But these nerves actually provide direct access to the brain.” The focused ultrasound then activates the microbubbles to expand and contract at the targeted brain site, where they act as a pump to enhance the local accumulation of the gold nanoclusters. The intranasal delivery reduces drug toxicity by preventing the encapsulated drugs from circulating throughout the entire body.

Although this study was conducted in mice, the team hopes to soon demonstrate its efficacy for patients with DIPG. The group will continue this work with nanoparticle and aerosol expert, Pratim Biswas, PhD, to scale up the technique from a mouse to a large animal model.

This exciting news received media coverage in Medgadget, InPharma Technologist, and Technology Networks’ 7 Days in Cancer Research, among others.

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