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

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.

• Authors: S Maya, Lekshmi G Kumar, Bruno Sarmento, N Sanoj Rejinold, Deepthy Menon, Shantikumar V Nair, R Jayakumar
• Journal: Carbohydrate polymers (Carbohydr Polym) Vol. 93 Issue 2 Pg. 661-9 (Apr 02 2013) ISSN: 1879-1344 [Electronic] England
• PMID: 23499109 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

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