Targeted ErbB3 cancer therapy: A synergistic approach to effectively combat cancer

Int J Pharm. 2020 Feb 15:575:118961. doi: 10.1016/j.ijpharm.2019.118961. Epub 2019 Dec 14.

Abstract

Surface modification of nanoparticles with aptamer is gaining popularity lately due to its selective targeting and low immunogenicity. In this study, sorafenib tosylate (SFB) was loaded in biodegradable PLGA nanoparticles prepared by solvent evaporation method. The surfaces of drug deprived and drug-loaded particles (PN and PNS, respectively) were coupled with aptamer to target ErbB3 using EDC/NHS chemical modification. Nanoparticles were characterized with regard to their size, shape and chemical composition by dynamic light scattering, atomic force microscopy, FTIR and elemental analysis respectively. To evaluate the particles in vitro cell culture studies were performed. Cell viability assay, pathway analysis and apoptosis assay showed cellular toxicity in the presence of aptamer in PNS-Apt (p < 0.001). Metastatic progression assay showed decreased cell migration in the presence of aptamer and SFB. Confocal laser scanning microscopy was used to visualize the receptor-mediated time-dependent intracellular uptake and distribution of the nanoparticles throughout the cytoplasm. The findings of the current study demonstrated the potential efficacy of the surface modified SFB-loaded particles against ErbB3.

Keywords: Aptamer; Cytotoxicity; Nanoparticles; PLGA; Sorafenib.

MeSH terms

  • Apoptosis / drug effects
  • Aptamers, Nucleotide / administration & dosage
  • Aptamers, Nucleotide / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Carriers / chemistry*
  • Humans
  • Nanoparticles / chemistry*
  • Particle Size
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Receptor, ErbB-3 / antagonists & inhibitors*
  • Sorafenib / administration & dosage
  • Sorafenib / pharmacology*
  • Technology, Pharmaceutical / methods

Substances

  • Aptamers, Nucleotide
  • Drug Carriers
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Sorafenib
  • Receptor, ErbB-3