I-Corps: Translation Potential of an Ultrasound-Triggered Drug Delivery to the Brain

Award ID: 2629187

This I-Corps project is based on the development of a non-invasive device for targeted drug delivery to the brain using ultrasound-responsive nanoparticles. Treatments that target the brain are limited because therapeutic agents cannot effectively cross the blood-brain barrier or produce unacceptable side effects when administered at the doses required to reach the brain. This technology combines intravenously administered nanoparticles with focused ultrasound to deliver therapeutic agents selectively to targeted brain regions, improving treatment precision while minimizing off-target exposure in healthy tissues. In addition, the platform is flexible and can be adapted to therapeutic payloads and disease indications. This may accelerate development of safer and more effective brain therapeutics. This I-Corps project utilizes experiential learning coupled with first-hand investigation of the industry ecosystem to assess the translation potential of focused ultrasound-cleavable hydrogen-bonded organic framework (HOF) nanoparticles for spatially controlled drug delivery across the blood-brain barrier. Current liposomal drug delivery systems often have composition and release characteristics that are constrained by lipid membrane properties. This technology employs chemically tunable HOF nanoparticles that encapsulate therapeutic payloads and release them in response to low-intensity focused ultrasound. In addition, HOF nanoparticles are built from modular crystalline building blocks whose chemistry can be readily tailored to control cargo loading, structural stability, and ultrasound responsiveness. This tunability enables a single delivery platform to accommodate various classes of therapeutics while providing localized, on-demand release following focused ultrasound exposure. Previous research demonstrated nanoparticle stability, favorable biocompatibility, and region-specific delivery in preclinical models. By combining chemically programmable nanoparticles with image-guided focused ultrasound, this technology may improve the precision, versatility, and translational applicability of targeted drug delivery for a broad range of central nervous system disorders. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Program Director: Ruth Shuman