RRC ID 44636
Author Lai CK, Lu YL, Hsieh JT, Tsai SC, Feng CL, Tsai YS, Tsai PC, Su HL, Lin YH, Lai CH.
Title Development of chitosan/heparin nanoparticle-encapsulated cytolethal distending toxin for gastric cancer therapy.
Journal Nanomedicine (Lond)
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.
Volume 9(6)
Pages 803-17
Published 2014-5-1
DOI 10.2217/nnm.13.54
PMID 24024568
MeSH Antineoplastic Agents / administration & dosage* Antineoplastic Agents / pharmacology Apoptosis / drug effects Bacterial Toxins / administration & dosage* Bacterial Toxins / pharmacology Cell Line, Tumor Cells, Cultured Chitosan / chemistry* Delayed-Action Preparations / chemistry* Gastric Mucosa / metabolism Heparin / chemistry* Humans Hydrogen-Ion Concentration Immunosuppressive Agents / administration & dosage Immunosuppressive Agents / pharmacology Nanoparticles / chemistry* Stomach / drug effects Stomach / pathology Stomach Neoplasms / drug therapy* Stomach Neoplasms / metabolism Stomach Neoplasms / pathology
IF 4.3
Times Cited 15
WOS Category BIOTECHNOLOGY & APPLIED MICROBIOLOGY NANOSCIENCE & NANOTECHNOLOGY
Resource
Human and Animal Cells