Dual-Labeled Near-Infrared/(99m)Tc Imaging Probes Using PAMAM-Coated Silica Nanoparticles for the Imaging of HER2-Expressing Cancer Cells

Int J Mol Sci. 2016 Jul 7;17(7):1086. doi: 10.3390/ijms17071086.

Abstract

We sought to develop dual-modality imaging probes using functionalized silica nanoparticles to target human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer cells and achieve efficient target imaging of HER2-expressing tumors. Polyamidoamine-based functionalized silica nanoparticles (PCSNs) for multimodal imaging were synthesized with near-infrared (NIR) fluorescence (indocyanine green (ICG)) and technetium-99m ((99m)Tc) radioactivity. Anti-HER2 antibodies were bound to the labeled PCSNs. These dual-imaging probes were tested to image HER2-overexpressing breast carcinoma cells. In vivo imaging was also examined in breast tumor xenograft models in mice. SK-BR3 (HER2 positive) cells were imaged with stronger NIR fluorescent signals than that in MDA-MB231 (HER2 negative) cells. The increased radioactivity of the SK-BR3 cells was also confirmed by phosphor imaging. NIR images showed strong fluorescent signals in the SK-BR3 tumor model compared to muscle tissues and the MDA-MB231 tumor model. Automatic well counting results showed increased radioactivity in the SK-BR3 xenograft tumors. We developed functionalized silica nanoparticles loaded with (99m)Tc and ICG for the targeting and imaging of HER2-expressing cells. The dual-imaging probes efficiently imaged HER2-overexpressing cells. Although further studies are needed to produce efficient isotope labeling, the results suggest that the multifunctional silica nanoparticles are a promising vehicle for imaging specific components of the cell membrane in a dual-modality manner.

Keywords: 99mTc; HER2; ICG; MDA-MB231; NIR; SK-BR3; athymic mice; dual-imaging probe; silica nanoparticles; xenograft.

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Female
  • Humans
  • Hydrazines / chemistry
  • Immunohistochemistry
  • Indocyanine Green / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Multimodal Imaging
  • Nanoparticles / chemistry*
  • Polyamines / chemistry*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / chemistry
  • Receptor, ErbB-2 / metabolism*
  • Silicon Dioxide / chemistry
  • Spectroscopy, Near-Infrared
  • Technetium / chemistry*
  • Transplantation, Heterologous

Substances

  • Alexa 488 hydrazide
  • Hydrazines
  • Poly(amidoamine)
  • Polyamines
  • Radiopharmaceuticals
  • Technetium
  • Silicon Dioxide
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Indocyanine Green