•  
  •  
 
Nano Research

Article Title

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

Authors

Geoffrey Bartholomeusz, Department of Experimental Therapeutics, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA
Paul Cherukuri, Department of Experimental Therapeutics, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA Department of Chemistry, Center for Biological and Environmental Nanotechnology, and Institute of Biosciences and Bioengineering, Rice University, 6100 Main Street, Houston, TX 77005, USA
John Kingston, Department of Experimental Therapeutics, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA
Laurent Cognet, Department of Chemistry, Center for Biological and Environmental Nanotechnology, and Institute of Biosciences and Bioengineering, Rice University, 6100 Main Street, Houston, TX 77005, USA Centre de Physique Moléculaire Optique et Hertzienne, Université Bordeaux 1 and CNRS, 351 cours de la Libération, 33405 Talence Cedex, France
Robert Lemos Jr., Department of Experimental Therapeutics, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA
Tonya K. Leeuw, Department of Chemistry, Center for Biological and Environmental Nanotechnology, and Institute of Biosciences and Bioengineering, Rice University, 6100 Main Street, Houston, TX 77005, USA
Laura Gumbiner-Russo, Department of Experimental Therapeutics, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA
R. Bruce Weisman, Department of Chemistry, Center for Biological and Environmental Nanotechnology, and Institute of Biosciences and Bioengineering, Rice University, 6100 Main Street, Houston, TX 77005, USA
Garth Powis, Department of Experimental Therapeutics, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA

Keywords

siRNA, single-walled carbon nanotubes, anti-cancer therapy, in vivo delivery agent

Abstract

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.

Graphical Abstract

Publisher

Tsinghua University Press

Share

COinS