The blood-brain barrier (BBB) is a natural barrier that protects the brain from substances that may be harmful to it. However, it can also prevent the delivery of therapeutic drugs to the brain. Researchers have found that using microbubbles (MBs) and focused ultrasound (FUS) can noninvasively, locally, and transiently open the BBB for the delivery of therapeutics. However, the oscillation of MBs is affected by blood vessel size, and they have been reported to be limited in small blood vessels due to their large diameter (1.5-4 μm). Our recent research has shown that the small diameter of capillaries in the brain’s vasculature, combined with the reduced MB oscillations in smaller blood vessels and lower MB concentration in capillaries, can limit BBB opening in small capillaries. This may hinder the effectiveness of therapeutic drug delivery.
To overcome this challenge, we have developed nanoscale theranostic nanobubbles (NBs) with a diameter of approximately 200 nm, which can easily enter capillaries. By using NBs in combination with low-frequency ultrasound, we believe that it may be possible to simultaneously open the BBB in both large and small blood vessels. The goal of this project is to optimize NB-mediated BBB opening for efficient delivery of therapeutics to the brain for the treatment of brain and CNS diseases. This research will also help to understand the interaction and impact of NB oscillations on blood vessels, which has the potential to pave the way for noninvasive theranostic approaches with applications in drug and gene delivery, neuroscience, radiology, immunology, cancer research, and more.
