Enhancing ultrasound-mediated cell membrane permeabilisation (sonoporation) using a high frequency pulse regime and implications for ultrasound-aided cancer chemotherapy

Cancer Lett. 2008 Aug 8;266(2):156-62. doi: 10.1016/j.canlet.2008.02.041. Epub 2008 Mar 25.

Abstract

Delivering ultrasound to HeLa cells at 1MHz using a high frequency pulse regime (40kHz) and at a maximum energy density of 270Jcm(-2) resulted in significant cell membrane permeabilisation. Using FITC-dextran as a fluorogenic marker, optimally up to 64% of treated populations were permeabilised with cell viability remaining above 80%. Although cell membrane permeabilisation was observed in the presence of the microbubble-based ultrasound contrast agent, SonoVue, cell viability was severely compromised. Using the high frequency pulse regime in the absence of microbubbles, the LD50 of the cancer chemotherapeutic agent, camptothecin, was reduced from 58 to 18nM.

MeSH terms

  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / metabolism
  • Antineoplastic Agents, Phytogenic / toxicity
  • Camptothecin / administration & dosage*
  • Camptothecin / metabolism
  • Camptothecin / toxicity
  • Cell Membrane Permeability
  • Combined Modality Therapy
  • Dextrans / metabolism
  • Fluorescein-5-isothiocyanate / analogs & derivatives
  • Fluorescein-5-isothiocyanate / metabolism
  • Fluorescent Dyes / metabolism
  • HeLa Cells
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / therapy
  • Ultrasonics*

Substances

  • Antineoplastic Agents, Phytogenic
  • Dextrans
  • Fluorescent Dyes
  • fluorescein isothiocyanate dextran
  • Fluorescein-5-isothiocyanate
  • Camptothecin