Liposomalized oligopeptides in cancer therapy

Organ-specific delivery of biofunctional agents is thought to enhance their activity and to reduce their side effects. Liposomes have been used as drug carriers in cancer chemotherapy, since they accumulate passively in tumor tissues due to an enhanced permeability and retention (EPR) effect. In addition, modification of liposomes with specific ligands enables active targeting. A small peptide having a high affinity for a certain antigen is suitable for modification of liposomes, since it is biocompatible, biodegradable, and less antigenic compared with antibody and other modifiers. Oligopeptide-modified liposomes are prepared by using lipophilic derivatives of the peptide, which are synthesized easily and incorporated readily into the liposomal bilayer. We describe two examples of the use of liposomal oligopeptides: one for antimetastatic therapy and the other for antineovascular therapy. Arg-Gly-Asp (RGD)-related peptides are known to contribute various cellular functions such as adhesion and invasion and to inhibit tumor metastasis. However, peptide drugs are generally rapidly hydrolyzed and eliminated from the bloodstream. Liposomal RGD enables the half-lives and affinity to be improved, resulting in enhancement of antimetastatic activity. We then describe the usefulness of liposomal Ala-Pro-Arg-Pro-Gly (APRPG) for tumor treatment, which is specific for tumor angiogenic vessels. APRPG is originally isolated by use of a phage-displayed peptide library. Adriamycin encapsulated in APRPG-modified liposomes accumulated specifically in and damage tumor neovessels, resulting in notable antitumor efficacy.