title: In vitro methods to study bubble-cell interactions: Fundamentals and therapeutic applications.
abstract: Besides their use as contrast agents for ultrasound imaging, microbubbles are increasingly studied for a wide range of therapeutic applications. In particular, their ability to enhance the uptake of drugs through the permeabilization of tissues and cell membranes shows great promise. In order to fully understand the numerous paths by which bubbles can interact with cells and the even larger number of possible biological responses from the cells, thorough and extensive work is necessary. In this review, we consider the range of experimental techniques implemented in in vitro studies with the aim of elucidating these microbubble-cell interactions. First of all, the variety of cell types and cell models available are discussed, emphasizing the need for more and more complex models replicating in vivo conditions together with experimental challenges associated with this increased complexity. Second, the different types of stabilized microbubbles and more recently developed droplets and particles are presented, followed by their acoustic or optical excitation methods. Finally, the techniques exploited to study the microbubble-cell interactions are reviewed. These techniques operate over a wide range of timescales, or even off-line, revealing particular aspects or subsequent effects of these interactions. Therefore, knowledge obtained from several techniques must be combined to elucidate the underlying processes.
authors: Physics of Fluids Group, MESA+ Institute for Nanotechnology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente , Enschede, The Netherlands.
authors: Guillaume
authors: G
authors: Lajoinie
authors: Laboratory of General Biochemistry and Physical Pharmacy, Ghent Research Group on Nanomedicines, Faculty of Pharmaceutical Sciences, Ghent University , Ghent, Belgium.
authors: Ine
authors: I
authors: De Cock
authors: Institute of Biomedical Engineering, University of Oxford , Oxford, United Kingdom.
authors: Constantin C
authors: CC
authors: Coussios
authors: Laboratory of General Biochemistry and Physical Pharmacy, Ghent Research Group on Nanomedicines, Faculty of Pharmaceutical Sciences, Ghent University , Ghent, Belgium.
authors: Ine
authors: 0000-0001-7492-6568
authors: I
authors: Lentacker
authors: MESA+ Institute for Nanotechnology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente , Enschede, The Netherlands.
authors: Séverine
authors: S
authors: Le Gac
authors: Institute of Biomedical Engineering, University of Oxford , Oxford, United Kingdom.
authors: Eleanor
authors: 0000-0003-3371-5929
authors: E
authors: Stride
authors: Physics of Fluids Group, MESA+ Institute for Nanotechnology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente , Enschede, The Netherlands.
authors: Michel
authors: M
authors: Versluis