Development of chitosan/heparin nanoparticle-encapsulated cytolethal distending toxin for gastric cancer therapy

Cheng Kuo Lai, Yu Luen Lu, Jer Tsong Hsieh, Shih Chang Tsai, Chun Lung Feng, Yuh Shyan Tsai, Pei Ching Tsai, Hong Lin Su, Yu Hsin Lin, Chih Ho Lai

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Aim: The aim of this work was to develop pH-responsive nanoparticles encapsulating CdtB and to demonstrate that these particles represent a potential therapeutic agent for gastric cancer. Materials & methods: Chitosan/heparin nanoparticle-encapsulated CdtB was prepared and the delivery efficiency was monitored by confocal laser scanning microscopy. The molecular basis of the nanoparticle-encapsulated CdtB-mediated p53 activation pathway was explored by immunoblot analysis. Antitumoral activities were investigated by analyzing the cell cycle and apoptosis. Results: Chitosan/heparin nanoparticle-encapsulated CdtB preferentially inhibited the proliferation of cells derived from gastric cancer, but not in primary gastric epithelial cells. Treatment of cells with nanoparticle-encapsulated CdtB enhanced cell-cycle arrest at G2/M, followed by apoptosis. Moreover, our data showed that the mechanism for nanoparticle- encapsulated CdtB-induced cell death was mediated by ATM-dependent DNA damage checkpoint responses. Conclusion: These findings indicate that chitosan/heparin nanoparticle-encapsulated CdtB could represent a new CdtB delivery strategy for the treatment of gastric cancer. Original submitted 8 May 2012; Revised submitted 5 February 201.

Original languageEnglish (US)
Pages (from-to)803-817
Number of pages15
JournalNanomedicine
Volume9
Issue number6
DOIs
StatePublished - Jun 2014

Keywords

  • apoptosis
  • cell cycle
  • chitosan
  • cytolethal distending toxin
  • heparin
  • nanoparticle

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science(all)

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  • Cite this

    Lai, C. K., Lu, Y. L., Hsieh, J. T., Tsai, S. C., Feng, C. L., Tsai, Y. S., Tsai, P. C., Su, H. L., Lin, Y. H., & Lai, C. H. (2014). Development of chitosan/heparin nanoparticle-encapsulated cytolethal distending toxin for gastric cancer therapy. Nanomedicine, 9(6), 803-817. https://doi.org/10.2217/nnm.13.54