Folate-mediated tumor cell targeting of liposome-entrapped doxorubicin in vitro

Robert J. Lee, Philip S. Low

Research output: Contribution to journalArticle

540 Scopus citations


Receptors for the vitamin folic acid are frequently overexpressed on epithelial cancer cells. To examine whether this overexpression might be exploited to specifically deliver liposome-encapsulated drug molecules in vitro, folate-targeted liposomes were prepared by incorporating 0.1 mol% of a folate-polyethyleneglycol-distearoylphosphatidylethanolamine (folate-PEG-DSPE) construct into the lipid bilayer, and were loaded with doxorubicin (DOX), an anti-cancer drug. Uptake of folate-PEG-liposomal DOX by KB cells was 45-fold higher than that of non-targeted liposomal DOX, and 1.6-times higher than that of free DOX, while the cytotoxicity was 86 and 2.7-times higher, respectively. Folate-targeting is fully compatible with PEG-coating of the liposomes, since incorporation of 4 mol% PEG2000-DSPE does not reduce the uptake or cytotoxicity of folate-PEG-liposomal DOX. Uptake of folate-PEG-liposomes was inhibited by 1 mM free folic acid but was unaffected by physiological concentrations of folate. In HeLa/W138 co-cultures, folate-PEG-liposomes encapsulating calcein, a fluorescent dye, were found to be almost exclusively internalized by the HeLa cells which overexpress the folate receptors. We suggest that folate targeting constitutes a possible mechanism for improving the specificity of PEG-coated liposomes for cancer cells.

Original languageEnglish (US)
Pages (from-to)134-144
Number of pages11
JournalBBA - Biomembranes
Issue number2
StatePublished - Feb 15 1995


  • Doxorubicin
  • Folate-binding protein
  • Liposome targeting
  • PEG-coated liposome
  • Tumor cell targeting

ASJC Scopus subject areas

  • Cell Biology
  • Biophysics
  • Biochemistry

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