Ultrasound-mediated disruption of the blood tumor barrier for improved therapeutic delivery

Neoplasia. 2021 Jul;23(7):676-691. doi: 10.1016/j.neo.2021.04.005. Epub 2021 Jun 14.

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.

Keywords: Blood-brain barrier; Blood-tumor barrier; Disruption; Drug delivery; Focused ultrasound; Permeability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Transport / radiation effects
  • Biological Variation, Population
  • Blood-Brain Barrier / metabolism*
  • Blood-Brain Barrier / radiation effects*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / etiology
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Disease Models, Animal
  • Drug Delivery Systems*
  • High-Intensity Focused Ultrasound Ablation / adverse effects
  • High-Intensity Focused Ultrasound Ablation / methods
  • Humans
  • Neoplasm Metastasis
  • Permeability / radiation effects
  • Treatment Outcome
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology
  • Tumor Microenvironment / radiation effects*
  • Ultrasonic Therapy
  • Ultrasonic Waves*