Single-walled carbon nanotubes-mediated in vivo and in vitro delivery of siRNA into antigen-presenting cells.
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.
Yang
R
R
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ryang@nankai.edu.cn
Yang
X
X
Zhang
Z
Z
Zhang
Y
Y
Wang
S
S
Cai
Z
Z
Jia
Y
Y
Ma
Y
Y
Zheng
C
C
Lu
Y
Y
Roden
R
R
Chen
Y
Y
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D018122:B7-1 Antigen / Q000032:analysis / Q000235:genetics; D015153:Blotting, Western / Q000379:methods; D005434:Flow Cytometry; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D037742:Nanotubes, Carbon; D009368:Neoplasm Transplantation; D010587:Phagocytosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000032:analysis / Q000235:genetics; D014162:Transfection / Q000379:methods
D018122:B7-1 Antigen; D037742:Nanotubes, Carbon; D034741:RNA, Small Interfering; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins