Ultrasound-Responsive Cavitation Nuclei for Therapy and Drug Delivery

Klazina Kooiman; Silke Roovers; Simone A G Langeveld; Robert T Kleven; Heleen Dewitte; Meaghan A O'Reilly; Jean-Michel Escoffre; Ayache Bouakaz; Martin D Verweij; Kullervo Hynynen; Ine Lentacker; Eleanor Stride; Christy K Holland

doi:10.1016/j.ultrasmedbio.2020.01.002

Ultrasound-Responsive Cavitation Nuclei for Therapy and Drug Delivery

Ultrasound Med Biol. 2020 Jun;46(6):1296-1325. doi: 10.1016/j.ultrasmedbio.2020.01.002. Epub 2020 Mar 10.

Authors

Affiliations

¹ Department of Biomedical Engineering, Thoraxcenter, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: k.kooiman@erasmusmc.nl.
² Ghent Research Group on Nanomedicines, Lab for General Biochemistry and Physical Pharmacy, Department of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
³ Department of Biomedical Engineering, Thoraxcenter, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁴ Department of Biomedical Engineering, College of Engineering and Applied Sciences, University of Cincinnati, Cincinnati, OH, USA.
⁵ Ghent Research Group on Nanomedicines, Lab for General Biochemistry and Physical Pharmacy, Department of Pharmaceutical Sciences, Ghent University, Ghent, Belgium; Laboratory for Molecular and Cellular Therapy, Medical School of the Vrije Universiteit Brussel, Jette, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent University, Ghent, Belgium.
⁶ Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
⁷ UMR 1253, iBrain, Université de Tours, Inserm, Tours, France.
⁸ Department of Biomedical Engineering, Thoraxcenter, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Laboratory of Acoustical Wavefield Imaging, Faculty of Applied Sciences, Delft University of Technology, Delft, The Netherlands.
⁹ Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada.
¹⁰ Ghent Research Group on Nanomedicines, Lab for General Biochemistry and Physical Pharmacy, Department of Pharmaceutical Sciences, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent University, Ghent, Belgium.
¹¹ Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, United Kingdom.
¹² Department of Biomedical Engineering, College of Engineering and Applied Sciences, University of Cincinnati, Cincinnati, OH, USA; Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati, Cincinnati, OH, USA.

Abstract

Therapeutic ultrasound strategies that harness the mechanical activity of cavitation nuclei for beneficial tissue bio-effects are actively under development. The mechanical oscillations of circulating microbubbles, the most widely investigated cavitation nuclei, which may also encapsulate or shield a therapeutic agent in the bloodstream, trigger and promote localized uptake. Oscillating microbubbles can create stresses either on nearby tissue or in surrounding fluid to enhance drug penetration and efficacy in the brain, spinal cord, vasculature, immune system, biofilm or tumors. This review summarizes recent investigations that have elucidated interactions of ultrasound and cavitation nuclei with cells, the treatment of tumors, immunotherapy, the blood-brain and blood-spinal cord barriers, sonothrombolysis, cardiovascular drug delivery and sonobactericide. In particular, an overview of salient ultrasound features, drug delivery vehicles, therapeutic transport routes and pre-clinical and clinical studies is provided. Successful implementation of ultrasound and cavitation nuclei-mediated drug delivery has the potential to change the way drugs are administered systemically, resulting in more effective therapeutics and less-invasive treatments.

Keywords: Blood–brain barrier opening; Bubble–cell interaction; Cavitation nuclei; Drug delivery; Sonobactericide; Sonoporation; Sonothrombolysis; Therapy; Tumor; Ultrasound.

Publication types

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

MeSH terms

Bacterial Infections / therapy
Blood-Brain Barrier
Cardiovascular Agents / administration & dosage
Drug Delivery Systems / methods*
Humans
Immunotherapy / methods
Microbubbles*
Neoplasms / therapy
Thrombolytic Therapy
Ultrasonic Therapy / methods*

Substances

Cardiovascular Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding