skip to main content

Title: Delivery of human NKG2D-IL-15 fusion gene by chitosan nanoparticles to enhance antitumor immunity

Nanoparticles are becoming promising carriers for gene delivery because of their high capacity in gene loading and low cell cytotoxicity. In this study, a chitosan-based nanoparticle encapsulated within a recombinant pcDNA3.1-dsNKG2D-IL-15 plasmid was generated. The fused dsNKG2D-IL-15 gene fragment consisted of double extracellular domains of NKG2D with IL-15 gene at downstream. The average diameter of the gene nanoparticles ranged from 200 nm to 400 nm, with mean zeta potential value of 53.8 ± 6.56 mV. The nanoparticles which were loaded with the dsNKG2D-IL-15 gene were uptaken by tumor cells with low cytotoxicity. Tumor cells pre-transfected by gene nanopartilces stimulated NK and T cells in vitro. Intramuscular injection of gene nanoparticles suppressed tumor growth and prolonged survival of tumor-bearing mice through activation of NK and CD8{sup +} T cells. Thus, chitosan-based nanoparticle delivery of dsNKG2D-IL-15 gene vaccine can be potentially used for tumor therapy. - Highlights: • Generation of a nanoparticle for delivery of dsNKG2D-IL-15 gene. • Characterization of the gene nanoparticle. • Antitumor activity mediated by the gene nanoparticle.
Authors:
; ;  [1] ;  [2] ;  [3] ;  [2] ;  [1] ;  [4] ;  [1] ;  [1] ;  [5] ;  [5] ;  [5] ;  [5]
  1. Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009 (China)
  2. Department of Gastroenterology, The Second Clinical Medical College, Yangzhou University, Yangzhou, 225009 (China)
  3. Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, 225009 (China)
  4. Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, 225009 (China)
  5. (China)
Publication Date:
OSTI Identifier:
22462122
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 463; Journal Issue: 3; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMINO ACIDS; ENZYMES; GENES; HISTOCOMPATIBILITY COMPLEX; IMMUNITY; IN VITRO; INTRAMUSCULAR INJECTION; LOADING; MICE; NANOPARTICLES; NEOPLASMS; OLIGOSACCHARIDES; PLANT GROWTH; THERAPY; TOXICITY; TUMOR CELLS; VACCINES