title: In Vivo Therapeutic Silencing of Hypoxia-Inducible Factor 1 Alpha (HIF-1α) Using Single-Walled Carbon Nanotubes Noncovalently Coated with siRNA.
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-1α 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.
authors.affiliation: Department of Experimental Therapeutics, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Bartholomeusz
authors.forename: Paul
authors.initials: P
authors.lastname: Cherukuri
authors.forename: John
authors.initials: J
authors.lastname: Kingston
authors.forename: Laurent
authors.initials: L
authors.lastname: Cognet
authors.forename: Robert
authors.initials: R
authors.lastname: Lemos
authors.forename: Tonya K
authors.initials: TK
authors.lastname: Leeuw
authors.forename: Laura
authors.initials: L
authors.lastname: Gumbiner-Russo
authors.forename: R Bruce
authors.initials: RB
authors.lastname: Weisman
authors.forename: Garth
authors.initials: G
authors.lastname: Powis