Acoustic Cluster Therapy (ACT®) enhances accumulation of polymeric micelles in the murine brain

The restrictive nature of the blood-brain barrier (BBB) prevents efficient treatment of many brain diseases. Focused ultrasound in combination with microbubbles has shown to safely and transiently increase BBB permeability. Here, the potential of Acoustic Cluster Therapy (ACT®), a microbubble platfo...

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Veröffentlicht in:Journal of controlled release 2021-09, Vol.337, p.285-295
Hauptverfasser: Olsman, Marieke, Mühlenpfordt, Melina, Olsen, Emma Bøe, Torp, Sverre H., Kotopoulis, Spiros, Rijcken, Cristianne J.F., Hu, Qizhi, Thewissen, Marielle, Snipstad, Sofie, de Lange Davies, Catharina
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container_end_page 295
container_issue
container_start_page 285
container_title Journal of controlled release
container_volume 337
creator Olsman, Marieke
Mühlenpfordt, Melina
Olsen, Emma Bøe
Torp, Sverre H.
Kotopoulis, Spiros
Rijcken, Cristianne J.F.
Hu, Qizhi
Thewissen, Marielle
Snipstad, Sofie
de Lange Davies, Catharina
description The restrictive nature of the blood-brain barrier (BBB) prevents efficient treatment of many brain diseases. Focused ultrasound in combination with microbubbles has shown to safely and transiently increase BBB permeability. Here, the potential of Acoustic Cluster Therapy (ACT®), a microbubble platform specifically engineered for theranostic purposes, to increase the permeability of the BBB and improve accumulation of IRDye® 800CW-PEG and core-crosslinked polymeric micelles (CCPM) in the murine brain, was studied. Contrast enhanced magnetic resonance imaging (MRI) showed increased BBB permeability in all animals after ACT®. Near infrared fluorescence (NIRF) images of excised brains 1 h post ACT® revealed an increased accumulation of the IRDye® 800CW-PEG (5.2-fold) and CCPM (3.7-fold) in ACT®-treated brains compared to control brains, which was retained up to 24 h post ACT®. Confocal laser scanning microscopy (CLSM) showed improved extravasation and penetration of CCPM into the brain parenchyma after ACT®. Histological examination of brain sections showed no treatment related tissue damage. This study demonstrated that ACT® increases the permeability of the BBB and enhances accumulation of macromolecules and clinically relevant nanoparticles to the brain, taking a principal step in enabling improved treatment of various brain diseases. [Display omitted] •ACT® safely and temporarily increased the permeability of the BBB in murine brains.•Increased brain accumulation of co-administered compounds was achieved upon ACT®.•ACT® enhanced extravasation and penetration of co-administered nanoparticles.•No treatment related tissue damage was observed.
doi_str_mv 10.1016/j.jconrel.2021.07.019
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subjects ACT
Blood-brain barrier
CCPM
Dual frequency transducer
Nanomedicine
Therapeutic ultrasound
title Acoustic Cluster Therapy (ACT®) enhances accumulation of polymeric micelles in the murine brain
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