Cancer treatment using an optically inert Rose Bengal derivative combined with pulsed focused ultrasound

Yoo Shin Kim, Valentina Rubio, Jianjun Qi, Rongmin Xia, Zheng Zheng Shi, Leif Peterson, Ching Hsuan Tung, Brian E. O'Neill

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Pulsed high intensity focused ultrasound (HIFU) has been combined with a photo-insensitive Rose Bengal derivative (RB2) to provide a synergistic cytotoxicity requiring the presence of both ultrasonic cavitation and drug. In vitro tests have shown that a short treatment (less than 30 s) of pulsed HIFU with peak negative pressure > 7 MPa (~ 27 W acoustic power at 1.4 MHz) destroys > 95% of breast cancer cells MDA-MB-231 in suspension with > 10 μM of the compound. Neither the pulsed HIFU nor the RB2 compound was found to have any significant impact on the viability of the cells when used alone. Introducing an antioxidant (N-acetylcysteine) reduced the effectiveness of the treatment. In vivo tests using these same cells growing as a xenograft in nu/nu mice were also done. An ultrasound contrast agent (Optison) and lower frequency (1.0 MHz) was used to help initiate cavitation at the tumor site. We were able to demonstrate tumor regression with cavitation alone, however, addition of RB2 compound injected i.v. yielded a substantial synergistic improvement.

Original languageEnglish (US)
Pages (from-to)315-322
Number of pages8
JournalJournal of Controlled Release
Volume156
Issue number3
DOIs
StatePublished - Dec 20 2011

Keywords

  • Cavitation
  • High intensity ultrasound (HIFU)
  • Optison
  • Rose Bengal
  • Sonodynamic therapy

ASJC Scopus subject areas

  • Pharmaceutical Science

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