Anti-VCAM-1 and Anti-IL4Rα Aptamer-Conjugated Super Paramagnetic Iron Oxide Nanoparticles for Enhanced Breast Cancer Diagnosis and Therapy

Molecules. 2020 Jul 29;25(15):3437. doi: 10.3390/molecules25153437.

Abstract

The surface protein overexpressed on cancer cells can be used as biomarkers for early detection of specific diseases. Anti-VCAM-1 and anti-IL4Rα DNA aptamers specific to VCAM-1 and IL4Rα receptors that are overexpressed in 4T1 tumor-bearing mice could be used as potential biomarker for both diagnostic and therapeutic applications in cancer biology. Cell Viability and luciferase assay of 4T1-Luc2 cancer cells in the presence of anti-VCAM-1 ssDNA or anti-IL4Rα RNA aptamers was assessed by monitoring the changes in the absorbance and the fluorescence of Alamar blue dye. The aptamer-conjugated SPIO magnetic beads, used for the selective targeting to tumor sites, were monitored using noninvasive MRI and Bioluminescence imaging (BLI). Cell viability and luciferase assays showed that both anti-VCAM-1 and anti-IL4Rα aptamers favor the depletion of cancer cells and limit tumor progression. Microscopic analyses confirmed that the target specific aptamers significantly trigger tumor cell apoptosis and limit cancer cell growth in vitro. The intravenous injection of SPIO nanoparticle-conjugated aptamers were further confirmed using noninvasive MRI and Bioluminescence imaging. Anti-VCAM1 and anti-IL4Rα aptamers, specific to VCAM-1 and IL4Rα receptors overexpressed in 4T1-Luc2 tumor-bearing mice, were used as diagnostic and therapeutic tools.

Keywords: BLI and SPION; IL4Rα aptamer; MRI; VCAM1 aptamer; luciferase assay; tumor imaging.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Aptamers, Nucleotide / administration & dosage*
  • Aptamers, Nucleotide / chemistry
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / etiology
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Female
  • Genes, Reporter
  • Humans
  • Interleukin-4 Receptor alpha Subunit / antagonists & inhibitors*
  • Luminescent Measurements
  • Magnetic Iron Oxide Nanoparticles* / chemistry
  • Magnetic Resonance Imaging
  • Mice
  • Theranostic Nanomedicine* / methods
  • Vascular Cell Adhesion Molecule-1 / antagonists & inhibitors*
  • Xenograft Model Antitumor Assays

Substances

  • Aptamers, Nucleotide
  • IL4R protein, human
  • Interleukin-4 Receptor alpha Subunit
  • Vascular Cell Adhesion Molecule-1