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

Robert J. Lee, Philip S. Low

Research output: Contribution to journalArticlepeer-review

560 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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