title: Folate receptor targeted delivery of liposomal daunorubicin into tumor cells.
abstract: BACKGROUND
  The folate receptor (FR) is amplified in a wide variety of human tumors. Thus, targeting cytotoxic therapies to FR is a promising strategy for chemotherapy.
  
  
  METHODS
  FR-targeted liposomal daunorubicin (f-L-DNR) was compared to non-targeted liposomal DNR (L-DNR) for cellular uptake and cytotoxicity in FR-expressing cells. Liposomal DNR retention was evaluated for liposomes loaded with either sodium citrate or ammonium sulfate as the trapping agent. The cellular uptake of liposomal DNR was determined by flow cytometry and fluorometry measurements while cytotoxicity was determined by the 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
  
  
  RESULTS
  Liposomal DNR retention was superior for liposomes prepared using ammonium sulfate. Cellular uptake of f-L-DNR in KB oral carcinoma cells, Chinese hamster ovary (CHO-FR-beta), and KG-1 human acute myelogenous leukemia cells were 9.4, 40, and 4,6-fold higher than non-targeted L-DNR, respectively. The cytotoxicity of f-L-DNR in KB and CHO-FR-beta cells was 18 times and 49 times higher than L-DNR, respectively. Both cellular uptake and cytotoxicity of f-L-DNR could be inhibited by 1 mM folic acid.
  
  
  CONCLUSIONS
  FR-mediated delivery of liposomal DNR to FR-expressing cells increases DNR cellular uptake and cytotoxicity. Therefore, therapeutic evaluation in relevant animal models is warranted.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus 43210, USA.
authors.forename: Sandy
authors.initials: S
authors.lastname: Ni
authors.forename: Stacy M
authors.initials: SM
authors.lastname: Stephenson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D001692:Biological Transport; D002352:Carrier Proteins / Q000187:drug effects*; D003630:Daunorubicin / Q000493:pharmacokinetics*; D004337:Drug Carriers; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D007624:KB Cells; D007700:Kinetics; D008081:Liposomes; D011956:Receptors, Cell Surface; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D002352:Carrier Proteins; D004337:Drug Carriers; D058973:Folate Receptors, GPI-Anchored; D008081:Liposomes; D011956:Receptors, Cell Surface; D005492:Folic Acid; D003630:Daunorubicin