Journal
NANO RESEARCH
Volume 2, Issue 4, Pages 279-291Publisher
TSINGHUA UNIV PRESS
DOI: 10.1007/s12274-009-9026-7
Keywords
siRNA; single-walled carbon nanotubes; anti-cancer therapy; in vivo delivery agent
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Funding
- NIH [CA-77204, CA-109552]
- Welch Foundation [C-0807]
- NSF Center for Biological and Environmental Nanotechnology [EEC-0647452]
- Alliance for NanoHealth [JSC-NNJ06HC25G]
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A new approach is described for delivering small interfering RNA (siRNA) into cancer cells by noncovalently complexing unmodified siRNA with pristine single-walled carbon nanotubes (SWCNTs). The complexes were prepared by simple sonication of pristine SWCNTs in a solution of siRNA, which then served both as the cargo and as the suspending agent for the SWCNTs. When complexes containing siRNA targeted to hypoxia-inducible factor 1 alpha (HIF-1 alpha) were added to cells growing in serum containing culture media, there was strong specific inhibition of cellular HIF-1 alpha activity. The ability to obtain a biological response to SWCNT/siRNA complexes was seen in a wide variety of cancer cell types. Moreover, intratumoral administration of SWCNT-HIF-1 alpha siRNA complexes in mice bearing MiaPaCa-2/HRE tumors significantly inhibited the activity of tumor HIF-1 alpha. As elevated levels of HIF-1 alpha are found in many human cancers and are associated with resistance to therapy and decreased patient survival, these results imply that SWCNT/siRNA complexes may have value as therapeutic agents.
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