Safe, transient and localized blood brain barrier (BBB) opening is essential for
therapeutic delivery to the brain for a variety of brain diseases, since the BBB creates an obstacle to effective drug delivery. The BBB normally excludes drugs that measure 0.4 kDa or more. In recent years, focused ultrasound (FUS) has emerged as a noninvasive therapeutic approach that enables the treatment of the brain at low frequencies (below 650 kHz) that can penetrate an intact human skull. When low energy FUS is combined with intravenously injected microbubbles (MBs);
i.e., efficient theranostic probes that concurrently serve as contrast agents and therapeutic agents,
the BBB opens in a noninvasive and localized manner, thus enabling drug delivery to the brain.
Our main goal is to optimize MB-mediated BBB opening for efficient delivery of
therapeutics across the BBB for noninvasive brain therapy, including brain cancer and
neurodegenerative diseases (i.e. Alzheimer’s and Parkinson’s disease). This can be
utilized for delivery of molecules of various pharmacologically-relevant sizes, including
large particles, biomarkers and lipid nanoparticles, which are highly investigated
therapeutics in different fields of brain therapy. Overall, we envision that this project
has the potential to significantly improve brain health, paving the way for truly
noninvasive theranostic approaches, with applications in many biomedical domains.
In-vivo setup. The mouse was mechanically positioned at the focal spot of an US transducer, located at the bottom of a water tank, using a custom holder
Microscopy images of brain slices. Blood vessels appear in green, while extravasated Evans Blue (EB) is red. MB+FUS treated brain demonstrating EB extravasation to the perivascular area.