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

Brandon S. Brown, Tariq Patanam, Keyan Mobli, Christian Celia, Peter E. Zage, Andrew J. Bean, Ennio Tasciotti

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)851-861
Number of pages11
JournalCancer Biology and Therapy
Volume15
Issue number7
DOIs
StatePublished - Jul 2014

Keywords

  • 3F8
  • Drug delivery
  • Etoposide
  • GD2
  • Immunoliposome
  • Nanomedicine
  • Neuroblastoma

ASJC Scopus subject areas

  • Oncology
  • Molecular Medicine
  • Pharmacology
  • Cancer Research

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