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Enzyme-Degradable Hybrid Polymer/Silica Microbubbles as Ultrasound Contrast Agents
Nadia H Tsao1, Elizabeth A H Hall1
1Institute of Biotechnology, Department of Chemical Engineering and Biotechnology, University of Cambridge , Tennis Court Road, Cambridge CB2 1QT, United Kingdom.
Langmuir : the ACS Journal of Surfaces and Colloids
|June 2, 2016
Summary
Researchers developed enzyme-degradable polymer/silica hybrid microbubbles for ultrasound imaging. These novel microbubbles offer tunable acoustic properties and efficient enzymatic degradation, showing promise for advanced diagnostic applications.
Area of Science:
- Materials Science
- Biomedical Engineering
- Acoustics
Background:
- Development of advanced ultrasound contrast agents is crucial for improved diagnostic imaging.
- Enzyme-degradable materials offer targeted clearance and reduced systemic exposure.
- Polymer-silica hybrids present opportunities for tunable material properties.
Purpose of the Study:
- To fabricate and characterize enzyme-degradable polymer/silica hybrid microbubbles.
- To investigate the effect of polymer content on microbubble structure, elasticity, and acoustic properties.
- To evaluate the enzyme degradability and ultrasound contrast performance of the hybrid microbubbles.
Main Methods:
- Synthesis of triethoxysilane end-capped polycaprolactone (SiPCL) and its incorporation into silica microbubbles using a polystyrene template.
- Characterization of microbubble composition, surface properties, and shell thickness using varying SiPCL feed ratios (75, 85, 95 wt %).
- Assessment of enzyme degradability by lipase and ultrasound contrast imaging at varying mechanical indices (MI).
Main Results:
- Hybrid microbubbles exhibited a layered structure with SiPCL-rich inner and outer layers and a silica-rich middle layer.
- Microbubble shell thickness was dependent on TEOS concentration and reaction time.
- Efficient degradation by lipase was observed, with stability in the absence of the enzyme.
- Ultrasound contrast intensity generally increased with SiPCL content, though 95 wt % SiPCL bubbles showed collapse.
- A nonlinear frequency response (third harmonic) emerged at higher MI, with the transition threshold increasing as SiPCL content decreased.
Conclusions:
- Enzyme-degradable polymer/silica hybrid microbubbles can be fabricated with tunable properties.
- The layered structure and SiPCL content influence acoustic responsiveness and stability.
- These microbubbles demonstrate potential as enzyme-responsive ultrasound contrast agents with tunable nonlinear acoustic behavior.

