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Removal of ligand-bound liposomes from cell surfaces by microbubbles exposed to ultrasound

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Abstract

Gas-filled microbubbles attached to cell surfaces can interact with focused ultrasound to create microstreaming of nearby fluid. We directly observed the ultrasound/microbubble interaction and documented that under certain conditions fluorescent particles that were attached to the surface of live cells could be removed. Fluorescently labeled liposomes that were larger than 500 nm in diameter were attached to the surface of endothelial cells using cRGD targeting to αvβ3 integrin. Microbubbles were attached to the surface of the cells through electrostatic interactions. Images taken before and after the ultrasound exposure were compared to document the effects on the liposomes. When exposed to ultrasound with peak negative pressure of 0.8 MPa, single microbubbles and groups of isolated microbubbles were observed to remove targeted liposomes from the cell surface. Liposomes were removed from a region on the cell surface that averaged 33.1 μm in diameter. The maximum distance between a single microbubble and a detached liposome was 34.5 μm. Single microbubbles were shown to be able to remove liposomes from over half the surface of a cell. The distance over which liposomes were removed was significantly dependent on the resting diameter of the microbubble. Clusters of adjoining microbubbles were not seen to remove liposomes. These observations demonstrate that the fluid shear forces generated by the ultrasound/microbubble interaction can remove liposomes from the surfaces of cells over distances that are greater than the diameter of the microbubble.

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Funding

The study was supported by Grant Numbers T32 CA121938, R25 CA153915 NCI, and 5U54CA119335-05 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. Support was also provided by the UCSD Cancer Center Specialized Support Grant P30 CA23100.

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Authors and Affiliations

  1. Department of Bioengineering, Moores Cancer Center, University of California San Diego, 3855 Health Sciences Dr. # 0815, La Jolla, CA, 92093-0815, USA

    Stuart Ibsen, Carolyn Schutt & Viviana Serra

  2. Department of Biology, University of California San Diego, La Jolla, CA, 92093, USA

    Ruben Mora

  3. Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA

    Guixin Shi & Wenjin Cui

  4. Department of Nanoengineering, Moores Cancer Center, University of California at San Diego, La Jolla, CA, 92093, USA

    Michael Benchimol & Sadik Esener

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  1. Stuart Ibsen
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  2. Ruben Mora
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  3. Guixin Shi
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  4. Carolyn Schutt
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  5. Wenjin Cui
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  6. Michael Benchimol
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  7. Viviana Serra
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  8. Sadik Esener
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Correspondence to Stuart Ibsen.

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Ibsen, S., Mora, R., Shi, G. et al. Removal of ligand-bound liposomes from cell surfaces by microbubbles exposed to ultrasound. J Biol Phys 43, 493–510 (2017). https://doi.org/10.1007/s10867-017-9465-4

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  • DOI: https://doi.org/10.1007/s10867-017-9465-4

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