Tumor cell targeting of liposome-entrapped drugs with phospholipid-anchored folic acid-PEG conjugates.
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.
Gabizon
Alberto
A
Oncology Department, Shaare Zedek Medical Center, Hebrew University School of Medicine, Jerusalem, Israel. alberto@md.huji.ac.il
Shmeeda
Hilary
H
Horowitz
Aviva T
AT
Zalipsky
Samuel
S
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*
D000970:Antineoplastic Agents; D008081:Liposomes; D010743:Phospholipids; D011092:Polyethylene Glycols; D005492:Folic Acid