Ultrasound-mediated disruption of the blood tumor barrier for improved therapeutic delivery
Tasneem Arsiwala, Samuel A. Sprowls, Kathryn E. Blethen, Chris E. Adkins, Pushkar Saralkar, Ross Fladeland, William H. Pentz, Antonio Gabriele, Brooke N. Kielkowski, Rashi I. Mehta, P. Wang, Jeffrey Carpenter, Manish Ranjan, Umer Najib, Ali R. Rezai, Paul R. Lockman
Abstract
The blood-brain barrier (BBB) is a major anatomical and physiological barrier limiting the passage of drugs into brain. Central nervous system tumors can impair the BBB by changing the tumor microenvironment leading to the formation of a leaky barrier, known as the blood-tumor barrier (BTB). Despite the change in integrity, the BTB remains effective in preventing delivery of chemotherapy into brain tumors. Focused ultrasound is a unique noninvasive technique that can transiently disrupt the BBB and increase accumulation of drugs within targeted areas of the brain. Herein, we summarize the current understanding of different types of targeted ultrasound mediated BBB/BTB disruption techniques. We also discuss influence of the tumor microenvironment on BBB opening, as well as the role of immunological response following disruption. Lastly, we highlight the gaps between evaluation of the parameters governing opening of the BBB/BTB. A deeper understanding of physical opening of the BBB/BTB and the biological effects following disruption can potentially enhance treatment strategies for patients with brain tumors.