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

JOURNAL OF CONTROLLED RELEASE

卷:337

Article

Olsman, Marieke¹  Muhlenpfordt, Melina¹  Olsen, Emma Boe¹  Torp, Sverre H.^2,3  Kotopoulis, Spiros^4,5  Rijcken, Cristianne J. F.⁶  Hu, Qizhi⁶  Thewissen, Marielle⁶  Snipstad, Sofie^1,7  Davies, Catharina de Lange¹ 

[1] Norwegian Univ Sci & Technol, Dept Phys, Trondheim, Norway

[2] Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway

[3] Trondheim Reg & Univ Hosp, St Olavs Hosp, Dept Pathol, Trondheim, Norway

[4] Haukeland Hosp, Natl Ctr Ultrasound Gastroenterol, Bergen, Norway

[5] Exact Therapeut, Oslo, Norway

[6] Cristal Therapeut, Maastricht, Netherlands

[7] St Olavs Hosp, Canc Clin, Trondheim, Norway

关键词: Therapeutic ultrasound;    Blood-brain barrier;    CCPM;    ACT (R);    Nanomedicine;    Dual frequency transducer;   

DOI  :  10.1016/j.jconrel.2021.07.019

来源: Elsevier

【 摘 要 】

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 (R)), a microbubble platform specifically engineered for theranostic purposes, to increase the permeability of the BBB and improve accumulation of IRDye (R) 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 (R). Near infrared fluorescence (NIRF) images of excised brains 1 h post ACT (R) revealed an increased accumulation of the IRDye (R) 800CW-PEG (5.2-fold) and CCPM (3.7-fold) in ACT (R)-treated brains compared to control brains, which was retained up to 24 h post ACT (R). Confocal laser scanning microscopy (CLSM) showed improved extravasation and penetration of CCPM into the brain parenchyma after ACT (R). Histological examination of brain sections showed no treatment related tissue damage. This study demonstrated that ACT (R) 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.

【 授权许可】

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