title: Epidermal growth factor receptor-targeted immunoliposomes for delivery of celecoxib to cancer cells.
abstract: Cyclooxygenase-2 (COX-2) is highly expressed in many different cancers. Therefore, the inhibition of the COX-2 pathway by a selective COX-2 inhibitor, celecoxib (CLX), may be an alternative strategy for cancer prevention and therapy. Liposomal drug delivery systems can be used to increase the therapeutic efficacy of CLX while minimizing its side effects. Previous studies have reported the encapsulation of CLX within the non-targeted long circulating liposomes and functional effect of these formulations against colorectal cancer cell lines. However, the selectivity and internalization of CLX-loaded liposomes can further be improved by grafting targeting ligands on their surface. Cetuximab (anti-epidermal growth factor receptor - EGFR - monoclonal antibody) is a promising targeting ligand since EGFR is highly expressed in a wide range of solid tumors. The aim of this study was to develop EGFR-targeted immunoliposomes for enhancing the delivery of CLX to cancer cells and to evaluate the functional effects of these liposomes in cancer cell lines. EGFR-targeted ILs, having an average size of 120nm, could encapsulate 40% of the CLX, while providing a sustained drug release profile. Cell association studies have also shown that the immunoliposome uptake was higher in EGFR-overexpressing cells compared to the non-targeted liposomes. In addition, the CLX-loaded-anti-EGFR immunoliposomes were significantly more toxic compared to the non-targeted ones in cancer cells with EGFR-overexpression but not in the cells with low EGFR expression, regardless of their COX-2 expression status. Thus, selective targeting of CLX with anti-EGFR immunoliposomes appears to be a promising strategy for therapy of tumors that overexpress EGFR.
authors.affiliation: Department of Biotechnology, Middle East Technical University, Ankara 06800, Turkey.
authors.forename: Yanuar Dwi Putra
authors.initials: YD
authors.lastname: Limasale
authors.affiliation: Department of Biotechnology, Middle East Technical University, Ankara 06800, Turkey; Department of Engineering Sciences, Middle East Technical University, Ankara 06800, Turkey; BIOMATEN, Center of Excellence in Biomaterials and Tissue Engineering, Middle East Technical University, Ankara 06800, Turkey.
authors.forename: Ayşen
authors.initials: A
authors.lastname: Tezcaner
authors.affiliation: Department of Biotechnology, Middle East Technical University, Ankara 06800, Turkey; BIOMATEN, Center of Excellence in Biomaterials and Tissue Engineering, Middle East Technical University, Ankara 06800, Turkey.
authors.forename: Can
authors.initials: C
authors.lastname: Özen
authors.affiliation: Department of Biotechnology, Middle East Technical University, Ankara 06800, Turkey; Department of Engineering Sciences, Middle East Technical University, Ankara 06800, Turkey; BIOMATEN, Center of Excellence in Biomaterials and Tissue Engineering, Middle East Technical University, Ankara 06800, Turkey.
authors.forename: Dilek
authors.initials: D
authors.lastname: Keskin
authors.affiliation: Department of Biotechnology, Middle East Technical University, Ankara 06800, Turkey; Department of Biological Sciences, Middle East Technical University, Ankara 06800, Turkey. Electronic address: banerjee@metu.edu.tr.
authors.forename: Sreeparna
authors.initials: S
authors.lastname: Banerjee
mesh_terms: D000068579:Celecoxib / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008081:Liposomes; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D008081:Liposomes; D051546:Cyclooxygenase 2; D066246:ErbB Receptors; D000068579:Celecoxib
keywords: Cancer; Celecoxib; EGFR; Immunoliposomes