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 language | English (US) |
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Pages (from-to) | 803-817 |
Number of pages | 15 |
Journal | Nanomedicine |
Volume | 9 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2014 |
Keywords
- apoptosis
- cell cycle
- chitosan
- cytolethal distending toxin
- heparin
- nanoparticle
ASJC Scopus subject areas
- Bioengineering
- Development
- Biomedical Engineering
- General Materials Science
- Medicine (miscellaneous)