Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells

Int J Mol Sci. 2021 Jul 1;22(13):7097. doi: 10.3390/ijms22137097.

Abstract

The application of siRNA in gene therapy is mainly limited because of the problems with its transport into cells. Utilization of cationic dendrimers as siRNA carriers seems to be a promising solution in overcoming these issues, due to their positive charge and ability to penetrate cell membranes. The following two types of carbosilane dendrimers were examined: CBD-1 and CBD-2. Dendrimers were complexed with pro-apoptotic siRNA (Mcl-1 and Bcl-2) and the complexes were characterized by measuring their zeta potential, circular dichroism and fluorescence of ethidium bromide associated with dendrimers. CBD-2/siRNA complexes were also examined by agarose gel electrophoresis. Both dendrimers form complexes with siRNA. Moreover, the cellular uptake and influence on the cell viability of the dendrimers and dendriplexes were evaluated using microscopic methods and XTT assay on MCF-7 cells. Microscopy showed that both dendrimers can transport siRNA into cells; however, a cytotoxicity assay showed differences in the toxicity of these dendrimers.

Keywords: carbosilane dendrimers; dendriplexes; nanocarriers; siRNA.

MeSH terms

  • Cations
  • Cell Survival
  • Circular Dichroism
  • Dendrimers / chemistry
  • Dendrimers / pharmacology
  • Genetic Therapy / methods
  • Humans
  • MCF-7 Cells
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism
  • Particle Size
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Double-Stranded / genetics
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / therapeutic use*
  • Silanes / chemistry
  • Silanes / metabolism
  • Silanes / pharmacology*

Substances

  • BCL2 protein, human
  • Cations
  • Dendrimers
  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Double-Stranded
  • RNA, Small Interfering
  • Silanes
  • carbosilane