title: Tumor cell targeting of liposome-entrapped drugs with phospholipid-anchored folic acid-PEG conjugates.
abstract: Targeting of liposomes with phospholipid-anchored folate conjugates is an attractive approach to deliver chemotherapeutic agents to folate receptor (FR) expressing tumors. The use of polyethylene glycol (PEG)-coated liposomes with folate attached to the outer end of a small fraction of phospholipid-anchored PEG molecules appears to be the most appropriate way to combine long-circulating properties critical for liposome deposition in tumors and binding of liposomes to FR on tumor cells. Although a number of important formulation parameters remain to be optimized, there are indications, at least in one ascitic tumor model, that folate targeting shifts intra-tumor distribution of liposomes to the cellular compartment. In vitro, folate targeting enhances the cytotoxicity of liposomal drugs against FR-expressing tumor cells. In vivo, the therapeutic data are still fragmentary and appear to be formulation- and tumor model-dependent. Further studies are required to determine whether folate targeting can confer a clear advantage in efficacy and/or toxicity to liposomal drugs.
authors.affiliation: Oncology Department, Shaare Zedek Medical Center, Hebrew University School of Medicine, Jerusalem, Israel. alberto@md.huji.ac.il
authors.forename: Alberto
authors.initials: A
authors.lastname: Gabizon
authors.forename: Hilary
authors.initials: H
authors.lastname: Shmeeda
authors.forename: Aviva T
authors.initials: AT
authors.lastname: Horowitz
authors.forename: Samuel
authors.initials: S
authors.lastname: Zalipsky
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D008081:Liposomes; D010743:Phospholipids / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D010743:Phospholipids; D011092:Polyethylene Glycols; D005492:Folic Acid