title: 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.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India.
authors.forename: S
authors.initials: S
authors.lastname: Maya
authors.forename: Lekshmi G
authors.initials: LG
authors.lastname: Kumar
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
authors.forename: N
authors.initials: N
authors.lastname: Sanoj Rejinold
authors.forename: Deepthy
authors.initials: D
authors.lastname: Menon
authors.forename: Shantikumar V
authors.initials: SV
authors.lastname: Nair
authors.forename: R
authors.initials: R
authors.lastname: Jayakumar
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D000068818:Cetuximab; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016503:Drug Delivery Systems / Q000379:methods*; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects / Q000648:ultrastructure; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods; D010078:Oxazines / Q000737:chemistry; D010316:Particle Size; D014966:Xanthenes / Q000737:chemistry
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C504164:O-carboxymethylchitosan; D010078:Oxazines; D014966:Xanthenes; C005843:resazurin; D048271:Chitosan; D066246:ErbB Receptors; D000068818:Cetuximab