Noncavitational mechanisms of interaction of ultrasound with targeted perfluorocarbon nanoparticles: Implications for drug delivery

Neelesh R. Soman, Jon N. Marsh, Michael S. Hughes, Gregory M. Lanza, Samuel A. Wickline

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

3 Scopus citations

Abstract

Perfluorocarbon (PFC) nanoparticles can serve as a very specific site-targeted contrast and therapeutic agent after binding to specific cellular biomarkers. Ultrasound has been used in conjunction with microbubbles to enhance the delivery of drugs and genes into the cell, mainly through the process of cavitation. We have demonstrated earlier that ultrasound at 2 MHz (1.9 MI) for 5 min can enhance the interaction of nanoparticles with targeted cells. In this study, we sought to establish that nanoparticles used in conjunction with ultrasound do not act as "cavitation" foci. Cell-culture inserts were seeded with human umbilical vein endothelial cells (HUVECs) and exposed to ultrasound in the presence of either Definity® or PFC nanoparticles. Definity® in conjunction with continuous wave ultrasound (2.25 MHz for 1 and 5 minutes) increased the permeability of monolayer by four to six times above the normal, decreased trans-endothelial electrical resistance (a sign of reduced membrane integrity), and decreased cell viability by ∼50%. Histological evaluation demonstrated extensive disruptions of cell monolayers. Nanoparticles (both non-targeted and targeted) elicited no changes in the measured parameters under similar insonification conditions. Sonically enhanced delivery of drugs from liquid perfluorocarbon nanoparticles to targeted cells does not involve cavitation but increased lipid exchange with targeted cells.

Original languageEnglish
Title of host publication2005 IEEE Ultrasonics Symposium
Pages1712-1715
Number of pages4
DOIs
StatePublished - Dec 1 2005
Event2005 IEEE Ultrasonics Symposium - Rotterdam, Netherlands
Duration: Sep 18 2005Sep 21 2005

Publication series

NameProceedings - IEEE Ultrasonics Symposium
Volume3
ISSN (Print)1051-0117

Conference

Conference2005 IEEE Ultrasonics Symposium
Country/TerritoryNetherlands
CityRotterdam
Period09/18/0509/21/05

Keywords

  • Cavitation
  • Contrast agent
  • Nanoparticles
  • Ultrasound

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