Ultrasound-Directed Drug Delivery

Postema, Michiel; Gilja, Odd Helge

doi:10.2174/138920107783018453

Cited by 89 publications

(65 citation statements)

References 86 publications

(135 reference statements)

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“…Almost 20 y ago, an original drug/gene delivery method based on ultrasound stimulation coupled with gaseous microbubbles was proposed (Bao et al 1997). On ultrasound exposure, microbubbles can oscillate, move, coalesce, fragment or otherwise be disrupted (Postema and Gilja 2007). These properties modify cell membrane permeability through a process known as sonoporation (Bao et al 1997;Miller et al 1999;Taniyama et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Efficient Gene Delivery by Sonoporation Is Associated with Microbubble Entry into Cells and the Clathrin-Dependent Endocytosis Pathway

Delalande

Leduc

Midoux

et al. 2015

Ultrasound in Medicine & Biology

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Microbubble oscillation at specific ultrasound settings leads to permeabilization of surrounding cells. This phenomenon, referred to as sonoporation, allows for the in vitro and in vivo delivery of extracellular molecules, including plasmid DNA. To date, the biological and physical mechanisms underlying this phenomenon are not fully understood. The aim of this study was to investigate the interactions between microbubbles and cells, as well as the intracellular routing of plasmid DNA and microbubbles, during and after sonoporation. High-speed imaging and fluorescence confocal microscopy of HeLa cells stably expressing enhanced green fluorescent protein fused with markers of cellular compartments were used for this investigation. Soft-shelled microbubbles were observed to enter cells during sonoporation using experimental parameters that led to optimal gene transfer. They interacted with the plasma membrane in a specific area stained with fluorescent cholera subunit B, a marker of lipid rafts. This process was not observed with hard-shelled microbubbles, which were not efficient in gene delivery under our conditions. The plasmid DNA was delivered to late endosomes after 3 h post-sonoporation, and a few were found in the nucleus after 6 h. Gene transfer efficacy was greatly inhibited when cells were treated with chlorpromazine, an inhibitor of the clathrin-dependent endocytosis pathway. In contrast, no significant alteration was observed when cells were treated with filipin III or genistein, both inhibitors of the caveolin-dependent pathway. This study emphasizes that microbubble-cell interactions do not occur randomly during sonoporation; microbubble penetration inside cells affects the efficacy of gene transfer at specific ultrasound settings; and plasmid DNA uptake is an active mechanism that involves the clathrin-dependent pathway.

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Section: Introductionmentioning

confidence: 99%

Efficient Gene Delivery by Sonoporation Is Associated with Microbubble Entry into Cells and the Clathrin-Dependent Endocytosis Pathway

Delalande

Leduc

Midoux

et al. 2015

Ultrasound in Medicine & Biology

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“…Sonoporation, the transient formation of micron-sized pores in cell membranes induced by ultrasound in combination with microbubbles is of great interest for targeted drug and gene delivery [2]. This technique shows promise in cancer treatment as it allows increased localised drug delivery [3,4].…”

Section: Introductionmentioning

confidence: 99%

Acoustically Active Antibubbles

et al. 2015

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In this study, we analyse the behaviour of antibubbles when subjected to an ultrasonic pulse. Specically, we derive oscillating behaviour of acoustic antibubbles with a negligible outer shell, resulting in a RayleighPlesset equation of antibubble dynamics. Furthermore, we compare theoretical behaviour of antibubbles to behaviour of regular gas bubbles. We conclude that antibubbles and regular bubbles respond to an acoustic wave in a very similar manner if the antibubble's liquid core radius is less than half the antibubble radius. For larger cores, antibubbles demonstrate highly harmonic behaviour, which would make them suitable vehicles in ultrasonic imaging and ultrasound-guided drug delivery.

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“…9 To date, there has been little examination of the various endocytic pathways (macropinocytosis or clathrin-or caveolinmediated) that may be involved in low energy ultrasound facilitation, 9,10 and it has been widely expected that pore formation is the initiating event. 11,12 However, few of these studies included any evaluation of endocytic mechanisms, and most were performed at acoustic pressures that would induce cavitation.…”

Section: Pore Formation and Endocytosismentioning

confidence: 99%