Cetuximab conjugated O-carboxymethyl chitosan nanoparticles for targeting EGFR overexpressing cancer cells

Carbohydr Polym. 2013 Apr 2;93(2):661-9. doi: 10.1016/j.carbpol.2012.12.032. Epub 2013 Jan 18.

Abstract

Nanoparticle mediated delivery of antineoplastic agents, functionalized with monoclonal antibodies has achieved extraordinary potential in cancer therapy. The objective of this study was to develop a drug delivery system comprising O-carboxymethyl chitosan (O-CMC) nanoparticles, surface-conjugated with Cetuximab (Cet) for targeted delivery of paclitaxel (PTXL) to Epidermal Growth Factor Receptor (EGFR) over-expressing cancer cells. Nanoparticles around 180±35nm and negatively charged were prepared through simple ionic gelation technique. The alamar blue assay indicated that these targeted nanoparticles displayed a superior anticancer activity compared to non-targeted nanoparticles. The nanoformulation triggered enhanced cell death (confirmed by flow cytometry) due to its higher cellular uptake. The selective uptake of Cet-PTXL-O-CMC nanoparticles by EGFR +VE cancer cells (A549, A431 and SKBR3) compared to EGFR -VE MIAPaCa-2 cells confirms the active targeting and delivery of PTXL via the targeted nanomedicine. Cet-PTXL-O-CMC nanoparticles can be used a promising candidate for the targeted therapy of EGFR over expressing cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / chemistry
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antineoplastic Agents / administration & dosage
  • Biomarkers, Tumor / metabolism
  • Cell Death
  • Cell Line, Tumor
  • Cetuximab
  • Chemistry, Pharmaceutical / methods
  • Chitosan / administration & dosage
  • Chitosan / analogs & derivatives*
  • Drug Delivery Systems / methods*
  • Drug Screening Assays, Antitumor
  • ErbB Receptors / metabolism*
  • Erythrocytes / drug effects
  • Erythrocytes / ultrastructure
  • Hemolysis / drug effects
  • Humans
  • Microscopy, Electron, Scanning
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Nanotechnology / methods
  • Oxazines / chemistry
  • Particle Size
  • Xanthenes / chemistry

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • O-carboxymethylchitosan
  • Oxazines
  • Xanthenes
  • resazurin
  • Chitosan
  • ErbB Receptors
  • Cetuximab