A novel DDS strategy, “dual-targeting”, and its application for antineovascular therapy

Dual-targeting liposomes modified with Ala-Pro-Arg-Pro-Gly (APRPG) and Gly-Asn-Gly-Arg-Gly (GNGRG) peptides were developed. They remarkably associated to growing human umbilical vein endothelial cells (HUVECs) compared with single-targeting liposomes modified with APRPG or GNGRG. Doxorubicin (DOX) encapsulated in the dual-targeting liposomes significantly suppressed the growth of HUVECs compared with that in single-targeting liposomes. The dual-targeting liposomes containing DOX strongly suppressed tumor growth in Colon26 NL-17 carcinoma-bearing mice. Confocal microscopic data indicated that this anticancer effect was brought by the association of these liposomes to angiogenic vessels in the tumor. These findings suggest that “dual-targeting” would be a hopeful method for targeting therapies.