Development of ligand-targeted liposomes for cancer therapy.
The continued evolution of targeted liposomal therapeutics has resulted in new agents with remarkable antitumour efficacy and relatively mild toxicity profiles. A careful selection of the ligand is necessary to reduce immunogenicity, retain extended circulation lifetimes, target tumour-specific cell surface epitopes, and induce internalisation and subsequent release of the therapeutic substance from the liposome. Methods for assembling targeted liposomes, including a novel micellar insertion technology, for incorporation of targeting molecules that efficiently transforms a non-targeted liposomal therapeutic to a targeted one, greatly assist the translation of targeted liposome technology into the clinic. Targeting strategies with liposomes directed at solid tumours and vascular targets are discussed. The authors believe the development of ligand-targeted liposomes is now in the advanced stage and offers unique and important advantages among other targeted therapies. Anti-HER2 immunoliposomal doxorubicin is awaiting Phase I clinical trials, the results of which should provide new insights into the promise of ligand-targeted liposomal therapies.
Noble
Charles O
CO
University of California at San Francisco, CA 94143, USA.
Kirpotin
Dmitri B
DB
Hayes
Mark E
ME
Mamot
Christoph
C
Hong
Keelung
K
Park
John W
JW
Benz
Christopher C
CC
Marks
James D
JD
Drummond
Daryl C
DC
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends*; D006801:Humans; D008024:Ligands; D008081:Liposomes; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D008024:Ligands; D008081:Liposomes