title: Etoposide-loaded immunoliposomes as active targeting agents for GD2-positive malignancies.
abstract: Systemic chemotherapeutics remain the standard of care for most malignancies even though they frequently suffer from narrow therapeutic index, poor serum solubility, and off-target effects. In this study, we have encapsulated etoposide, a topoisomerase inhibitor effective against a wide range of cancers, in surface-modified liposomes decorated with anti-GD2 antibodies. We characterized the properties of the liposomes using a variety of methods including dynamic light scattering, electron microscopy, and Fourier transformed infrared spectroscopy. We examined whether these immunoliposomes were able to target cell lines expressing varying levels of surface GD2 and affect cellular proliferation. Anti-GD2 liposomes were generally targeted in a manner that correlated with GD2 expression and inhibited proliferation in cell lines to which they were efficiently targeted. The mechanism by which the immunoliposomes entered targeted cells appeared to be via clathrin-dependent uptake as demonstrated using flow cytometry and confocal microscopy. These studies suggest that anti-GD2-targeted, etoposide-loaded liposomes represent a potential strategy for more effective delivery of anti-cancer drugs that could be used for GD2 positive tumors.
authors.affiliation: Department of Neurobiology and Anatomy and Graduate School of Biomedical Sciences; The University of Texas Health Science Center at Houston; Houston, TX USA; Department of Nanomedicine; The Methodist Hospital Research Institute; Houston, TX USA.
authors.forename: Brandon S
authors.initials: BS
authors.lastname: Brown
authors.affiliation: Department of Nanomedicine; The Methodist Hospital Research Institute; Houston, TX USA.
authors.forename: Tariq
authors.initials: T
authors.lastname: Patanam
authors.affiliation: Department of Neurobiology and Anatomy and Graduate School of Biomedical Sciences; The University of Texas Health Science Center at Houston; Houston, TX USA; Department of Nanomedicine; The Methodist Hospital Research Institute; Houston, TX USA.
authors.forename: Keyan
authors.initials: K
authors.lastname: Mobli
authors.affiliation: Department of Nanomedicine; The Methodist Hospital Research Institute; Houston, TX USA; Department of Pharmacy; University "G. d'Annunzio" of Chieti; Pescara, Chieti, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Celia
authors.affiliation: Dan L. Duncan Cancer Center; Baylor College of Medicine; Houston, TX USA; Section of Hematology-Oncology; Department of Pediatrics; Texas Children's Cancer Center; Baylor College of Medicine; Houston, TX USA.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Zage
authors.affiliation: Department of Neurobiology and Anatomy and Graduate School of Biomedical Sciences; The University of Texas Health Science Center at Houston; Houston, TX USA; Division of Pediatrics; The University of Texas M.D. Anderson Cancer Center; Houston, TX USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Bean
authors.affiliation: Department of Nanomedicine; The Methodist Hospital Research Institute; Houston, TX USA.
authors.forename: Ennio
authors.initials: E
authors.lastname: Tasciotti
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis; D005047:Etoposide / Q000008:administration & dosage* / Q000494:pharmacology; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D008081:Liposomes; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D059003:Topoisomerase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: C419226:3F8 antibody; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D002966:Clathrin; D005732:Gangliosides; D007074:Immunoglobulin G; D008081:Liposomes; D059003:Topoisomerase Inhibitors; C019403:ganglioside, GD2; D005047:Etoposide
keywords: 3F8; GD2; drug delivery; etoposide; immunoliposome; nanomedicine; neuroblastoma
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