Nanoencapsulated anti-CK2 small molecule drug or siRNA specifically targets malignant cancer but not benign cells

Cancer Lett. 2012 Feb 1;315(1):48-58. doi: 10.1016/j.canlet.2011.10.007. Epub 2011 Oct 12.

Abstract

CK2, a pleiotropic Ser/Thr kinase, is an important target for cancer therapy. We tested our novel tenfibgen-based nanocapsule for delivery of the inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) and an siRNA directed against both CK2α and α' catalytic subunits to prostate cancer cells. We present data on the TBG nanocapsule itself and on CK2 inhibition or downregulation in treated cells, including effects on Nuclear Factor-kappa B (NF-κB) p65. By direct comparison of two CK2-directed cargos, our data provide proof that the TBG encapsulation design for delivery of drugs specifically to cancer cells has strong potential for small molecule- and nucleic acid-based cancer therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Benzimidazoles / administration & dosage*
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacokinetics
  • Casein Kinase II / antagonists & inhibitors*
  • Casein Kinase II / genetics*
  • Casein Kinase II / metabolism
  • Cell Growth Processes / drug effects
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Down-Regulation
  • Humans
  • Male
  • Mice
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / therapy*
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / pharmacokinetics
  • Transfection

Substances

  • 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole
  • Benzimidazoles
  • RNA, Small Interfering
  • Casein Kinase II