BARTHOLOMEUSZ, Geoffrey; CHERUKURI, Paul; KINGSTON, John; COGNET, Laurent; LEMOS, Robert Jr.; LEEUW, Tonya; GUMBINER-RUSSO, Laura; WEISMAN, R. Bruce; POWIS, Garth

doi:10.1007/s12274-009-9026-7

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BARTHOLOMEUSZ, Geoffrey
Department of Experimental Therapeutics

CHERUKURI, Paul
Department of Experimental Therapeutics
Department of Chemistry

KINGSTON, John
Department of Experimental Therapeutics

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Nano Research. 2009-04-17, vol. 2, n° 4, p. 279-291

Springer

Résumé en anglais

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.< Réduire

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siRNA

single-walled carbon nanotubes

anti-cancer therapy

in vivo delivery agent

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

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