Ultrasound-triggered oxygen-loaded nanodroplets enhance and monitor cerebral damage from sonodynamic therapy

Nanotheranostics

article

Harriet Lea-Banks¹  Sheng-Kai Wu¹  Hannah Lee¹  Kullervo Hynynen¹ 

[1] Physical Sciences Platform, Sunnybrook Research Institute;Department of Medical Biophysics, University of Toronto;Institute of Biomedical Engineering, University of Toronto

关键词: ultrasound;    cavitation;    phase-change emulsion;    microbubble;   

DOI  :  10.7150/ntno.71946

学科分类：大气科学

来源: Ivyspring International Publisher

【 摘 要 】

In sonodynamic therapy, cellular toxicity from sonosensitizer drugs, such as 5-aminolevulinic acid hydrochloride (5-ALA), may be triggered with focused ultrasound through the production of reactive oxygen species (ROS). Here we show that by increasing local oxygen during treatment, using oxygen-loaded perfluorocarbon nanodroplets (250 +/- 8 nm), we can increase the damage induced by 5-ALA, and monitor the severity by recording acoustic emissions in the brain. To achieve this, we sonicated the right striatum of 16 healthy rats after an intravenous dose of 5-ALA (200 mg/kg), followed by saline, nanodroplets, or oxygen-loaded nanodroplets. We assessed haemorrhage, edema and cell apoptosis immediately following, 24 hr, and 48 hr after focused ultrasound treatment. The localized volume of damaged tissue was significantly enhanced by the presence of oxygen-loaded nanodroplets, compared to ultrasound with unloaded nanodroplets (3-fold increase), and ultrasound alone (40-fold increase). Sonicating 1 hr following 5-ALA injection was found to be more potent than 2 hr following 5-ALA injection (2-fold increase), and the severity of tissue damage corresponded to the acoustic emissions from droplet vaporization. Enhancing the local damage from 5-ALA with monitored cavitation activity and additional oxygen could have significant implications in the treatment of atherosclerosis and non-invasive ablative surgeries.

【 授权许可】

CC BY-NC