1. ¹Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
2. ²Key Laboratory of Bioactive Materials, Department of Immunology, College of Medicine, Ministry of Education, Nankai University, Tianjin, China
3. ³Institute of Polymer Chemistry and Key Laboratory for Functional Polymer Materials, College of Chemistry, Nankai University, Tianjin, China
4. ⁴China Clinical Laboratory, Tianjin Chest Hospital, Tianjin, China
5. ⁵Department of Mathematics, China Civil Aviation University, Tianjin, China

Correspondence: Dr R Yang or Y Chen, Department of Immunology, College of Medicine, Nankai University, Weijin Road 94, Tianjin 300071, China. E-mails: ryang@nankai.edu.cn or yschen99@nankai.edu.cn

⁶These authors contributed equally to this work.

Received 26 January 2006; Revised 2 May 2006; Accepted 5 May 2006; Published online 6 July 2006.

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.