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Shear stress preconditioning and microbubble flow pattern modulate ultrasound-assisted plasma membrane
Elahe Memari1, Brandon Helfield1,2
1Department of Physics, Concordia University, Montreal, H4B 1R6, Canada.
Materials Today. Bio
|July 11, 2024
Summary
Microbubble-mediated focused ultrasound enhances targeted drug delivery for ischemic heart disease. Endothelial cell responses to ultrasound depend on blood flow conditions, influencing therapy effectiveness.
Area of Science:
- Cardiovascular Research
- Biomedical Engineering
- Cellular Biology
Background:
- Targeted drug delivery for ischemic heart disease (e.g., atherosclerosis) is limited by the lack of site-specific therapeutic deposition.
- Microbubble-mediated focused ultrasound offers a promising approach to enhance local endothelial permeability for drug delivery.
- Understanding microbubble-endothelial cell interactions under disturbed blood flow is crucial for optimizing this therapy.
Purpose of the Study:
- To investigate microbubble-mediated endothelial permeabilization under various physiological conditions using focused ultrasound.
- To examine the influence of endothelial preconditioning and different blood flow patterns on ultrasound therapy efficacy.
- To correlate treatment outcomes with specific cytokine and chemokine levels.
Main Methods:
- Utilized an acoustically-coupled microscopy system to sonicate endothelial cells with Definity™ microbubbles.
- Applied ultrasound (1 MHz, 20 cycle bursts, 1 ms PRI, 4 s duration, 300 kPa peak-negative pressure) under controlled perfusion conditions.
- Investigated effects of prolonged shear, non-reversing pulsatile flow, and reversing oscillatory flow on endothelial permeabilization.
Main Results:
- Endothelial preconditioning under prolonged shear altered the secretome, increasing pro-angiogenic analytes and decreasing pro-inflammatory ones, enhancing ultrasound susceptibility.
- Ultrasound treatment efficiency positively correlated with pro-angiogenic cytokines (VEGF-A, EGF, FGF-2) and negatively with pro-inflammatory chemokines (MCP-1, GCP-2, SDF-1).
- Non-reversing pulsatile flow increased endothelial permeabilization up to 2.4-fold compared to laminar flow; reversing oscillatory flow showed heterogeneous modulation.
Conclusions:
- Vascular physiology and endothelial biology significantly impact localized ultrasound drug delivery systems for ischemic heart disease.
- Optimizing ultrasound parameters and understanding flow dynamics are key to enhancing therapeutic deposition.
- This research provides critical insights for designing more effective targeted therapies for cardiovascular conditions.
