Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (B). Efficiency of pharmacological action

Int J Pharm. 2015 May 15;485(1-2):288-94. doi: 10.1016/j.ijpharm.2015.03.034. Epub 2015 Mar 18.

Abstract

This paper examines a perspective to use newly engineered nanomaterials as effective and safe carriers for gene therapy of cancer. Three different groups of cationic dendrimers (PAMAM, phosphorus, and carbosilane) were complexed with anticancer siRNA and the biophysical properties of the dendriplexes created were analyzed. The potential of the dendrimers as nanocarriers for anticancer Bcl-xl, Bcl-2, Mcl-1 siRNAs and additionally a scrambled sequence siRNA has been explored. Dendrimer/siRNA complexes were characterised by various methods including fluorescence, zeta potential, dynamic light scattering, circular dichroism, gel electrophoresis and transmission electron microscopy. In this part of study, the transfection of complexes in HeLa and HL-60 cells was analyzed using both single apoptotic siRNAs and a mixture (cocktail) of them. Cocktails were more effective than single siRNAs, allowing one to decrease siRNAs concentration in treating cells. The dendrimers were compared as siRNA carriers, the most effective being the phosphorus-based ones. However, they were also the most cytotoxic on their own, so that in this regard the application of all dendrimers in anticancer therapy will be discussed.

Keywords: Anticancer siRNA; Cancer cells; Dendrimer; Nano-drug-delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Survival
  • Circular Dichroism
  • Dendrimers / chemistry*
  • Dendrimers / toxicity
  • Electrophoresis, Agar Gel
  • Gene Expression Regulation, Neoplastic
  • HL-60 Cells
  • HeLa Cells
  • Heparin / chemistry
  • Humans
  • Light
  • Microscopy, Electron, Transmission
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Nucleic Acid Conformation
  • Particle Size
  • Phosphorus / chemistry*
  • Phosphorus / toxicity
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • RNAi Therapeutics / methods*
  • Scattering, Radiation
  • Silanes / chemistry*
  • Silanes / toxicity
  • Spectrometry, Fluorescence
  • Transfection / methods*
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism

Substances

  • BCL2 protein, human
  • BCL2L1 protein, human
  • Dendrimers
  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • PAMAM Starburst
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • Silanes
  • bcl-X Protein
  • carbosilane
  • Phosphorus
  • Heparin