title: EGFR targeted thermosensitive liposomes: A novel multifunctional platform for simultaneous tumor targeted and stimulus responsive drug delivery.
abstract: The epidermal growth factor receptor (EGFR) is a promising target for anti-cancer therapy. The aim of this study was to design thermosensitive liposomes (TSL), functionalized with anti-EGFR ligands for targeted delivery and localized triggered release of chemotherapy. For targeting, EGFR specific peptide (GE11) and Fab' fragments of cetuximab were used and the effect of ligand density on in vitro tumor targeting was investigated. Ligand conjugation did not significantly change the physicochemical characteristics of liposomes. Fab'-decorated TSL (Fab'-TSL) can specifically and more efficiently bind to the EGFR overexpressed cancer cells as compared to GE11 modified TSL. Calcein labeled Fab'-TSL showed adequate stability at 37°C in serum (<4% calcein released after 1h) and a temperature dependent release at above 40°C. FACS analysis and live cell imaging showed efficient and EGFR mediated cellular association as well as dramatic intracellular cargo release upon hyperthermia. Fab'-conjugation and hyperthermia induced enhanced tumor cell cytotoxicity of doxorubicin loaded TSL. The relative cytotoxicity of Fab'-TSL was also correlated to EGFR density on the tumor cells. These results suggest that Fab'-TSL showed great potential for combinational targeted and triggered release drug delivery.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Laboratory Experimental Surgical Oncology, Section Surgical Oncology, Department of Surgery, Erasmus MC Cancer Center, Rotterdam, The Netherlands. Electronic address: a_haeri@sbmu.ac.ir.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Haeri
authors.affiliation: Laboratory Experimental Surgical Oncology, Section Surgical Oncology, Department of Surgery, Erasmus MC Cancer Center, Rotterdam, The Netherlands.
authors.forename: Sara
authors.initials: S
authors.lastname: Zalba
authors.affiliation: Laboratory Experimental Surgical Oncology, Section Surgical Oncology, Department of Surgery, Erasmus MC Cancer Center, Rotterdam, The Netherlands. Electronic address: t.l.m.tenhagen@erasmusmc.nl.
authors.forename: Timo L M
authors.initials: TL
authors.lastname: Ten Hagen
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Simin
authors.initials: S
authors.lastname: Dadashzadeh
authors.affiliation: Laboratory Experimental Surgical Oncology, Section Surgical Oncology, Department of Surgery, Erasmus MC Cancer Center, Rotterdam, The Netherlands.
authors.forename: Gerben A
authors.initials: GA
authors.lastname: Koning
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000068818:Cetuximab / Q000737:chemistry / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D066246:ErbB Receptors / Q000008:administration & dosage* / Q000737:chemistry*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D008081:Liposomes / Q000737:chemistry*
chemical_list: D008081:Liposomes; D004317:Doxorubicin; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: Cetuximab; Epidermal growth factor receptor (EGFR); GE11 peptide; Hyperthermia; Targeting; Thermosensitive liposomes