Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 12, Issue -, Pages 3095-3107Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S128032
Keywords
NKG2D; IL-21; fusion gene; cancer; chitosan nanoparticle
Funding
- National Natural Science Foundation of China [81671547, 81471547, 81273214, 81172785]
- social development fund of Yangzhou municipality [YZ2014179]
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Nanoparticles can be loaded with exogenous DNA for the potential expression of cytokines with immune-stimulatory function. NKG2D identifies major histocompatibility complex class I chain-related protein in human and retinoic acid early induced transcript-1 in mouse, which acts as tumor-associated antigens. Biologic agents based on interleukin 21 (IL-21) have displayed antitumor activities through lymphocyte activation. The NKG2D-IL-21 fusion protein theoretically identifies tumor cells through NKG2D moiety and activates T cells through IL-21 moiety. In this study, double-gene fragments that encode the extracellular domains of NKG2D and IL-21 genes were connected and then inserted into the pcDNA3.1(-) plasmid. PcDNA3.1-dsNKG2D-IL-21 plasmid nanoparticles based on chitosan were generated. Tumor cells pretransfected with dsNKG2D IL-21 gene nanoparticles can activate natural killer (NK) and CD8(+) T cells in vitro. Serum IL-21 levels were enhanced in mice intramuscularly injected with the gene nanoparticles. DsNKG2D-IL-21 gene nanoparticles accumulated in tumor tissues after being intravenously injected for similar to 4-24 h. Treatment of dsNKG2D-IL-21 gene nanoparticles also retarded tumor growth and elongated the life span of tumor-bearing mice by activating NK and T cells in vivo. Thus, the dsNKG2D-IL-21 gene nanoparticles exerted efficient antitumor activities and would be potentially used for tumor therapy.
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