In Vivo Therapeutic Silencing of Hypoxia-Inducible Factor 1 Alpha (HIF-1\alpha) Using Single-Walled Carbon Nanotubes Noncovalently Coated with siRNA - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nano Research Année : 2009

In Vivo Therapeutic Silencing of Hypoxia-Inducible Factor 1 Alpha (HIF-1\alpha) Using Single-Walled Carbon Nanotubes Noncovalently Coated with siRNA

Résumé

A new approach is described for delivering small interfering RNA (siRNA) into cancer cells by noncovalently complexing unmodifi ed 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 hypoxiainducible 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 signifi cantly inhibited the activity of tumor HIF-1 . 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.

Dates et versions

hal-00505889 , version 1 (26-07-2010)

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Citer

Geoffrey Bartholomeusz, Paul Cherukuri, John Kingston, Laurent Cognet, Robert Jr. Lemos, et al.. In Vivo Therapeutic Silencing of Hypoxia-Inducible Factor 1 Alpha (HIF-1\alpha) Using Single-Walled Carbon Nanotubes Noncovalently Coated with siRNA. Nano Research, 2009, 2 (4), pp.279-291. ⟨10.1007/s12274-009-9026-7⟩. ⟨hal-00505889⟩

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