In vivo therapeutic silencing of hypoxia-inducible factor 1 alpha (HIF-1α) using single-walled carbon nanotubes noncovalently coated with siRNA
siRNA, single-walled carbon nanotubes, anti-cancer therapy, in vivo delivery agent
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.
Tsinghua University Press
Geoffrey Bartholomeusz,Paul Cherukuri,John Kingston,Laurent Cognet,Robert Lemos,Tonya K. Leeuw,Laura Gumbiner-Russo,R. Bruce Weisman,Garth Powis, In vivo therapeutic silencing of hypoxia-inducible factor 1 alpha (HIF-1α) using single-walled carbon nanotubes noncovalently coated with siRNA. NanoRes.2009, 2: 279-291