The labeling of cationic iron oxide nanoparticle-resistant hepatocellular carcinoma cells using targeted magnetoliposomes

Biomaterials. 2011 Feb;32(6):1748-58. doi: 10.1016/j.biomaterials.2010.11.005. Epub 2010 Nov 26.

Abstract

The in vitro labeling of cultured cells with nanomaterials is a frequent practice but the efficiency, specificity and cytotoxicity of labeling specific cell types using targeted nanoparticles has only rarely been investigated. In the present work, functionalized anionic lipid-coated iron oxide cores (magnetoliposomes (MLs)) bearing galactose moieties were used for the specific labeling of asialoglycoprotein receptor 1 (ASGPR-1)-expressing HepG2 cells. The optimal number of galactose moieties per particle (± 26) was determined and uptake efficiency was compared with galactose-lacking anionic and cationic MLs. Using a blocking assay with free galactose, electron microscopy and co-cultures of HepG2 and non-ASGPR-1 expressing C17.2 cells, the specificity of the particles for the ASGPR-1 receptor was demonstrated. The intracellular localization of the galactose-bearing MLs was further verified by confocal microscopy. The non-toxic ML concentration was determined to be 400 μg Fe/ml. Finally, the use of these MLs for visualization of labelled cells by magnetic resonance imaging (MRI) was demonstrated. The data show a high uptake and specificity of the galactose-bearing MLs, whereas the cationic MLs remain primarily surface-associated. Thus, targeted MLs offer a successful alternative for cell labeling when cationic particles fail to be efficiently internalized.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Carcinoma, Hepatocellular
  • Cell Line
  • Cell Proliferation
  • Cell Survival
  • Ferric Compounds / chemistry*
  • Ferric Compounds / metabolism
  • Hep G2 Cells
  • Humans
  • Liposomes / chemistry*
  • Mice
  • Nanoparticles / chemistry*
  • Reactive Oxygen Species / metabolism
  • Staining and Labeling / methods*
  • Transferrin / metabolism

Substances

  • Ferric Compounds
  • Liposomes
  • Reactive Oxygen Species
  • Transferrin
  • ferric oxide
  • Calcium