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In vivo therapeutic silencing of hypoxia-inducible factor 1 alpha (HIF-1α) using single-walled carbon nanotubes noncovalently coated with siRNA

Bartholomeusz, Geoffrey and Cherukuri, Paul and Kingston, John and Cognet, Laurent and Lemos, Robert and Leeuw, Tonya K. and Gumbiner-Russo, Laura and Weisman, R. Bruce and Powis, Garth (2009) In vivo therapeutic silencing of hypoxia-inducible factor 1 alpha (HIF-1α) using single-walled carbon nanotubes noncovalently coated with siRNA. Nano Research, 2 (4). pp. 279-291.

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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-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-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.

Item Type:Article
Subjects:Biomedical Science > Nanobiotechnology
ID Code:5118
Deposited By:CSMNT
Deposited On:17 Aug 2010 15:02
Last Modified:19 Aug 2010 11:14

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