Abstract
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 SOCS1siRNA 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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Acknowledgements
This work was supported by the ‘863’ project (Grant no. 2003AA302640) of the Ministry of Science and Technology of China, Postdocorate Funding (Grant no. 20040055020) of the Ministry of Education of China, NSF Funding (Grant no. 043803711) of Tianjin City, NSFC Funding (Grant no. 30540022) and Nankai University Funding.
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Yang, R., Yang, X., Zhang, Z. et al. Single-walled carbon nanotubes-mediated in vivo and in vitro delivery of siRNA into antigen-presenting cells. Gene Ther 13, 1714–1723 (2006). https://doi.org/10.1038/sj.gt.3302808
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DOI: https://doi.org/10.1038/sj.gt.3302808
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