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Dissipative Microgravimetry to Study the Binding Dynamics of the Phospholipid Binding Protein Annexin A2 to Solid-supported Lipid Bilayers Using a Quartz Resonator
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Lipid Shell Retention and Selective Binding Capability Following Repeated Transient Acoustic Microdroplet

Jennifer N Harmon1, Chloe A Celingant-Copie1, Foad Kabinejadian1

  • 1Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana 70118, United States.

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Summary

Activatable droplet contrast agents retain targeting ligands during repeated ultrasound vaporization. While some lipids shed, affecting droplet size, targeted therapy and molecular imaging accuracy remain unaffected.

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Area of Science:

  • Biomedical Engineering
  • Ultrasound Technology
  • Nanomedicine

Background:

  • Microbubble contrast agents are established for ultrasound-guided therapy and imaging.
  • Activatable droplet contrast agents offer enhanced functionality but their lipid shell behavior under repeated ultrasound exposure is not fully understood.
  • Understanding lipid shell dynamics is crucial for optimizing droplet-based contrast agents.

Purpose of the Study:

  • To investigate the retention of lipid shells in activatable droplet contrast agents after repeated vaporization events.
  • To assess the impact of lipid shell shedding on droplet size and targeting capabilities.
  • To evaluate the stability of PEGylated and non-PEGylated lipids during phase transitions.

Main Methods:

  • Utilized fluorescent markers to track PEGylated and non-PEGylated lipid subpopulations.
  • Employed confocal microscopy for initial lipid distribution analysis.
  • Applied high-speed optical imaging to observe repeated vaporization and recondensation under focused ultrasound.
  • Used flow cytometry to quantify lipid shedding and assess droplet targeting post-activation.

Main Results:

  • Droplets successfully underwent repeated vaporization and recondensation using focused ultrasound.
  • PEGylated lipids, including targeting ligands, were fully retained on the shell.
  • Approximately 20% of bulk (non-PEGylated) lipids were shed, leading to a reduced average droplet diameter.
  • Targeting capabilities of RGD peptide-functionalized droplets remained unaffected.

Conclusions:

  • Activatable droplet contrast agents exhibit robust retention of targeting ligands during repeated ultrasound activation.
  • While lipid shedding influences droplet size distribution, it does not compromise the accuracy of targeted therapy or molecular imaging.
  • These findings support the use of activatable droplet contrast agents for advanced ultrasound applications.