HER2-Targeted Multifunctional Silica Nanoparticles Specifically Enhance the Radiosensitivity of HER2-Overexpressing Breast Cancer Cells

Int J Mol Sci. 2018 Mar 19;19(3):908. doi: 10.3390/ijms19030908.

Abstract

We investigated the effects of targeted functionalized silica nanoparticles on the radiosensitivity of cancer cells. Better control of the local concentration of silica nanoparticles may facilitate their use as an adjuvant in conjunction with ionizing radiation to target cancer cells while preventing damage to normal cells. Hyperbranched polyamidoamine (PAMAM) was grafted onto the surface of amorphous silica nanoparticles to functionalize them. The PAMAM-coated silica nanoparticles (PCSNs) were then conjugated with fluorescent dyes. Anti-HER2 antibodies were covalently attached to the labeled PCSNs. The HER2-overexpressing SK-BR3 breast cancer cell line was incubated in medium containing the PCSN probes. After incubation; the cells were exposed to X-ray radiation. Cells were counted in all samples using cell proliferation assays; and apoptotic cells were detected. The cell survival results showed that the combination of the targeted PCSN probes and radiation reduced the survival rate of SK-BR3 cells to a greater extent than when either PCSN probes, PCSNs or radiation were applied individually. The results also showed an increase in apoptosis in the SK-BR3 cells that internalized the PCSN probes and were then irradiated. Based on these data, PCSN probes act as specific radiosensitizing agents for HER2-overexpressing cells.

Keywords: HER2; SK-BR3; radiosensitizer; silica nanoparticle.

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / radiotherapy
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Cell Survival
  • Female
  • Fluorescence
  • Humans
  • Lysosomes / metabolism
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Particle Size
  • Polyamines / chemistry
  • Radiation Tolerance*
  • Receptor, ErbB-2 / metabolism*
  • Silicon Dioxide / chemistry*

Substances

  • Poly(amidoamine)
  • Polyamines
  • Silicon Dioxide
  • Receptor, ErbB-2