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

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.