Single-walled carbon nanotubes-mediated in vivo and in vitro delivery of siRNA into antigen-presenting cells

R. Yang, X. Yang, Z. Zhang, Y. Zhang, S. Wang, Z. Cai, Y. Jia, Y. Ma, C. Zheng, Y. Lu, R. Roden, Y. Chen

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1714-1723
Number of pages10
JournalGene Therapy
Volume13
Issue number24
DOIs
StatePublished - Dec 2006

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Yang, R., Yang, X., Zhang, Z., Zhang, Y., Wang, S., Cai, Z., Jia, Y., Ma, Y., Zheng, C., Lu, Y., Roden, R., & Chen, Y. (2006). Single-walled carbon nanotubes-mediated in vivo and in vitro delivery of siRNA into antigen-presenting cells. Gene Therapy, 13(24), 1714-1723. https://doi.org/10.1038/sj.gt.3302808