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

摘要

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 hypoxia-inducible factor 1 alpha(HIF-1)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-1 siRNA complexes in mice bearing MiaPaCa-2/HRE tumors signifi cantly inhibited the activity of tumor HIF-1.As elevated levels of HIF-1 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.