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Cancer Biol Ther. 2014 Jul;15(7):851-61. doi: 10.4161/cbt.28875. Epub 2014 Apr 22.

Etoposide-loaded immunoliposomes as active targeting agents for GD2-positive malignancies.

Author information

1
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.
2
Department of Nanomedicine; The Methodist Hospital Research Institute; Houston, TX USA.
3
Department of Nanomedicine; The Methodist Hospital Research Institute; Houston, TX USA; Department of Pharmacy; University "G. d'Annunzio" of Chieti; Pescara, Chieti, Italy.
4
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.
5
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.

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.

KEYWORDS:

3F8; GD2; drug delivery; etoposide; immunoliposome; nanomedicine; neuroblastoma

PMID:
24755919
PMCID:
PMC4100986
DOI:
10.4161/cbt.28875
[Indexed for MEDLINE]
Free PMC Article

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