Sonic activation of molecularly-targeted nanoparticles accelerates transmembrane lipid delivery to cancer cells through contact-mediated mechanisms: Implications for enhanced local drug delivery

Kathryn C. Crowder, Michael S. Hughes, Jon N. Marsh, Alejandro M. Barbieri, Ralph W. Fuhrhop, Gregory M. Lanza, Samuel A. Wickline

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Liquid perfluorocarbon nanoparticles serve as sensitive and specific targeted contrast and drug delivery vehicles by binding to specific cell surface markers. We hypothesized that application of acoustic energy at diagnostic power levels could promote nanoparticle-associated drug delivery by stimulating increased interaction between the nanoparticle's lipid layer and the targeted cell's plasma membrane. Ultrasound (mechanical index = 1.9) applied with a conventional ultrasound imaging system to nanoparticles targeted to αvβ3-integrins on C32 melanoma cancer cells in vitro produced no untoward effects. Within 5 min, lipid delivery from nanoparticles into cell cytoplasm was dramatically augmented. We also demonstrate the operation of a potential physical mechanism for this effect, the acoustic radiation force on the nanoparticles, which may contribute to the enhanced lipid delivery. Accordingly, we propose that local delivery of lipophilic substances (e.g., drugs) from targeted nanoparticles directly into cell cytoplasm can be augmented rapidly and safely with conventional ultrasound imaging devices through nondestructive mechanisms.

Original languageEnglish
Pages (from-to)1693-1700
Number of pages8
JournalUltrasound in Medicine and Biology
Volume31
Issue number12
DOIs
StatePublished - Dec 2005

Keywords

  • Acoustic radiation forces
  • Contrast agent
  • Lipid exchange
  • Membrane fusion
  • Nanoparticle
  • Targeted drug delivery
  • Ultrasound

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