Local delivery system of cytotoxic agents to tumors by focused sonoporation

K. Iwanaga, K. Tominaga, K. Yamamoto, M. Habu, H. Maeda, S. Akifusa, T. Tsujisawa, T. Okinaga, J. Fukuda, T. Nishihara

Research output: Contribution to journalArticlepeer-review

116 Citations (Scopus)

Abstract

Recently, ultrasound-targeting microbubble destruction has been employed in molecular gene therapy, and a new potent nonviral gene transfer method known as 'sonoporation' has been developed. We investigated the efficiency of sonoporation toward growth inhibition of human gingival squamous carcinoma cell line, Ca9-22, in vitro and in vivo. The cytotoxicity of bleomycin (BLM) was investigated using flow-cytometric analysis and Hoechst's staining in vitro assay systems. We found that the delivery of BLM by sonoporation induced cytotoxic effect toward Ca9-22 cells in vitro. Our in vivo results showed that tumors nearly disappeared in Ca9-22 cell-implanted nude KSN/slc mice treated with a low dose of BLM followed by sonoporation during the 4-week experimental period. Histological analysis revealed that the cytotoxic effect was mainly apoptosis. We previously reported that the cytolethal distending toxin B (cdtB) from Actinobacillus actinomycetemcomitans, a periodontopathic bacterium, is responsible for cell cycle arrest and apoptosis in vitro. Thus, we used sonoporation to transfect a cdtB-expressing plasmid into Ca9-22 cells and examined cell viability in vitro and in vivo. We found that an administration of cdtB-expressing plasmid followed by sonoporation-induced marked growth inhibition of Ca9-22 cells and apoptotic cells were also observed in vitro and in vivo. These findings suggest that local administration of cytotoxic agents with sonoporation is a useful method for molecular cancer therapy.

Original languageEnglish
Pages (from-to)354-363
Number of pages10
JournalCancer Gene Therapy
Volume14
Issue number4
DOIs
Publication statusPublished - 2007 Apr
Externally publishedYes

Keywords

  • Apoptosis
  • In vivo transfection
  • Sonoporation
  • Squamous cell carcinoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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