Docetaxel immunonanocarriers as targeted delivery systems for HER 2-positive tumor cells: preparation, characterization, and cytotoxicity studies

Int J Nanomedicine. 2011:6:1903-12. doi: 10.2147/IJN.S23211. Epub 2011 Sep 8.

Abstract

Background: The objective of this study was to develop pegylated poly lactide-co-glycolide acid (PLGA) immunonanocarriers for targeting delivery of docetaxel to human breast cancer cells.

Methods: The polyethylene glycol (PEG) groups on the surface of the PLGA nanoparticles were functionalized using maleimide groups. Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2) antigens of cancer cells, used as the targeting moiety, was attached to the maleimide groups on the surface of pegylated PLGA nanoparticles. Nanoparticles prepared by a nanoprecipitation method were characterized for their size, size distribution, surface charge, surface morphology, drug-loading, and in vitro drug release profile.

Results: The average size of the trastuzumab-decorated nanoparticles was 254 ± 16.4 nm and their zeta potential was -11.5 ± 1.4 mV. The average size of the nontargeted PLGA nanoparticles was 183 ± 22 nm and their zeta potential was -2.6 ± 0.34 mV. The cellular uptake of nanoparticles was studied using both HER2-positive (SKBR3 and BT-474) and HER2-negative (Calu-6) cell lines.

Conclusion: The cytotoxicity of the immunonanocarriers against HER2-positive cell lines was significantly higher than that of nontargeted PLGA nanoparticles and free docetaxel.

Keywords: HER2 receptor; PLGA; docetaxel; drug targeting; immunonanocarriers; nanoparticles; trastuzumab.

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Agents / administration & dosage*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Docetaxel
  • Drug Carriers* / chemistry
  • Drug Delivery Systems
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Microscopy, Electron, Scanning
  • Nanomedicine
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Polyethylene Glycols
  • Polyglactin 910
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / immunology
  • Receptor, ErbB-2 / metabolism*
  • Taxoids / administration & dosage*
  • Trastuzumab

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Drug Carriers
  • Taxoids
  • poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer
  • Docetaxel
  • Polyglactin 910
  • Polyethylene Glycols
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab