title: Development of chitosan/heparin nanoparticle-encapsulated cytolethal distending toxin for gastric cancer therapy.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  These findings indicate that chitosan/heparin nanoparticle-encapsulated CdtB could represent a new CdtB delivery strategy for the treatment of gastric cancer.
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Cheng-Kuo
authors.initials: CK
authors.lastname: Lai
authors.forename: Yu-Luen
authors.initials: YL
authors.lastname: Lu
authors.forename: Jer-Tsong
authors.initials: JT
authors.lastname: Hsieh
authors.forename: Shih-Chang
authors.initials: SC
authors.lastname: Tsai
authors.forename: Chun-Lung
authors.initials: CL
authors.lastname: Feng
authors.forename: Yuh-Shyan
authors.initials: YS
authors.lastname: Tsai
authors.forename: Pei-Ching
authors.initials: PC
authors.lastname: Tsai
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Su
authors.forename: Yu-Hsin
authors.initials: YH
authors.lastname: Lin
authors.forename: Chih-Ho
authors.initials: CH
authors.lastname: Lai
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D005753:Gastric Mucosa / Q000378:metabolism; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry*; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; C067044:cytolethal distending toxin; D006493:Heparin; D048271:Chitosan
keywords: apoptosis; cell cycle; chitosan; cytolethal distending toxin; heparin; nanoparticle