Gene therapy based on interleukin-۱۲ loaded chitosan nanoparticles in a mouse model of fibrosarcoma

Objective(s): Interleukin-۱۲ (IL-۱۲) as a cytokine has been proved to have a critical role in stimulating the immune system and has been used as immunotherapeutic agents in cancer gene therapy. Chitosan as a polymer, with high ability of binding to nucleic acids is a good candidate for gene delivery since it is biodegradable, biocompatible and non-allergenic polysaccharide. The objective of the present study was to investigate the effects of cells transfected with IL-۱۲ loaded chitosan nanoparticles on the regression of fibrosarcoma tumor cells (WEHI-۱۶۴) in vivo. Materials and Methods: WEHI-۱۶۴ tumor cells were transfected with IL-۱۲ loaded chitosan nanoparticles and then were injected subcutaneously to inoculate tumor in BALB/c mice. Tumor volumes were determined and subsequently extracted after mice sacrifice. The immunohistochemistry staining was performed for analysis of Ki-۶۷ expression (a tumor proliferation marker) in tumor masses. The expression of IL-۱۲ and IFN-γ were studied using real-time polymerase chain reaction and immunoblotting. Results: The group treated with IL-۱۲ loaded chitosan nanoparticles indicated decreasing of tumor mass volume (P<۰.۰۰۱). The results of western blotting and real-time PCR showed that the IL-۱۲ expression was increased in the group. Immunohistochemistry staining indicated that the Ki-۶۷expression was reduced in the group treated with IL-۱۲ loaded chitosan nanoparticles. Conclusion: IL-۱۲ gene therapy using chitosan nanoparticles has therapeutic effects on the regression of tumor masses in fibrosarcoma mouse model.

Keywords:

Chitosan , Gene Therapy , IL-۱۲ , In vivo , Nanoparticle , Tumor