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Nano Research

, Volume 2, Issue 4, pp 279–291 | Cite as

In vivo therapeutic silencing of hypoxia-inducible factor 1 alpha (HIF-1α) using single-walled carbon nanotubes noncovalently coated with siRNA

  • Geoffrey Bartholomeusz
  • Paul Cherukuri
  • John Kingston
  • Laurent Cognet
  • Robert LemosJr.
  • Tonya K. Leeuw
  • Laura Gumbiner-Russo
  • R. Bruce Weisman
  • Garth Powis
Open Access
Research Article

Abstract

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-1α) were added to cells growing in serum containing culture media, there was strong specific inhibition of cellular HIF-1 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-1α siRNA complexes in mice bearing MiaPaCa-2/HRE tumors significantly inhibited the activity of tumor HIF-1α. As elevated levels of HIF-1α 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.

Keywords

siRNA single-walled carbon nanotubes anti-cancer therapy in vivo delivery agent 

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Copyright information

© Tsinghua University Press and Springer-Verlag GmbH 2009

Authors and Affiliations

  • Geoffrey Bartholomeusz
    • 1
  • Paul Cherukuri
    • 1
    • 2
  • John Kingston
    • 1
  • Laurent Cognet
    • 2
    • 3
  • Robert LemosJr.
    • 1
  • Tonya K. Leeuw
    • 2
  • Laura Gumbiner-Russo
    • 1
  • R. Bruce Weisman
    • 2
  • Garth Powis
    • 1
  1. 1.Department of Experimental TherapeuticsUniversity of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.Department of Chemistry, Center for Biological and Environmental Nanotechnology, and Institute of Biosciences and BioengineeringRice UniversityHoustonUSA
  3. 3.Centre de Physique Moléculaire Optique et HertzienneUniversité Bordeaux 1 and CNRSTalence CedexFrance

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