Journal
GENE THERAPY
Volume 13, Issue 24, Pages 1714-1723Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.gt.3302808
Keywords
single-walled carbon nanotubes; siRNA; dendritic cell; antigen-presenting cell
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Antigen-presenting cells such as dendritic cells (DCs) play a critical role in inducing and regulating immune responses. One effective strategy for DC-based immunotherapy is to regulate maturation and function of DC. In this study, we apply single-walled carbon nanotubes (SWNTs) to carry small interfering RNA (siRNA) to reach, enter and genetically modify DCs in vivo. We prepared positively charged SWNTs (SWNTs+) using 1,6-diaminohexane which was demonstrated by transmission electron microscopy equipped with energy-dispersive X-ray spectroscopy and atomic force microscope. The functionalized SWNTs+ could absorb siRNA to form complexes of siRNA with SWNTs. These siRNA: SWNT+ complexes were preferentially taken up by splenic CD11c+ DCs, CD11b+ cells and also Gr-1+CD11b+ cells comprising DCs, macrophages and other myeloid cells to silence the targeting gene. Suppressor of cytokine signaling 1 (SOCS1) restricts the ability of DCs to break self-tolerance and induce antitumor immunity. Infusion of SWNTs+ carrying SOCS1 siRNA reduced SOCS1 expression and retarded the growth of established B16 tumor in mice, indicating the possibility of in vivo immunotherapeutics using SWNTs-based siRNA transfer system.
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