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Publications

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review Ppublish 75 citations

PubMed: 34801617 DOI: 10.1016/j.addr.2021.114043

Towards controlled drug delivery in brain tumors with microbubble-enhanced focused ultrasound.

Adv Drug Deliv Rev 180:114043

Authors: Scott Schoen, M Sait Kilinc, Hohyun Lee, Yutong Guo, F Levent Degertekin, Graeme F Woodworth, Costas Arvanitis

Affiliations

  • Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
  • School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
  • Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, College Park, MD 20742, USA; Fischell Department of Bioengineering A. James Clarke School of Engineering, University of Maryland, USA.
  • Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA; Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.

Abstract

Brain tumors are particularly challenging malignancies, due to their location in a structurally and functionally distinct part of the human body - the central nervous system (CNS). The CNS is separated and protected by a unique system of brain and blood vessel cells which together prevent most bloodborne therapeutics from entering the brain tumor microenvironment (TME). Recently, great strides have been made through microbubble (MB) ultrasound contrast agents in conjunction with ultrasound energy to locally increase the permeability of brain vessels and modulate the brain TME. As we elaborate in this review, this physical method can effectively deliver a wide range of anticancer agents, including chemotherapeutics, antibodies, and nanoparticle drug conjugates across a range of preclinical brain tumors, including high grade glioma (glioblastoma), diffuse intrinsic pontine gliomas, and brain metastasis. Moreover, recent evidence suggests that this technology can promote the effective delivery of novel immunotherapeutic agents, including immune check-point inhibitors and chimeric antigen receptor T cells, among others. With early clinical studies demonstrating safety, and several Phase I/II trials testing the preclinical findings underway, this technology is making firm steps towards shaping the future treatments of primary and metastatic brain cancer. By elaborating on its key components, including ultrasound systems and MB technology, along with methods for closed-loop spatial and temporal control of MB activity, we highlight how this technology can be tuned to enable new, personalized treatment strategies for primary brain malignancies and brain metastases.

MeSH

Brain Neoplasms, Neoplasm Metastasis, Pharmaceutical Preparations, Cells, Therapeutics, Glioma, Technology, Blood, Microbubbles

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