Antiangiogenic cancer therapy using tumor vasculature-targeted liposomes encapsulating 3-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one, SU5416

Previously, we identified angiogenic vessel-homing peptide Ala-Pro-Arg-Pro-Gly (APRPG), and showed that APRPG-modified liposomes could selectively target to tumor neovasculature. Here, we designed an APRPG-modified liposome encapsulating SU5416, an angiogenesis inhibitor, to overcome the solubility problem, and to enhance the antiangiogenic activity of SU5416. Liposomal SU5416 appeared to have the appropriate characteristics, such as particle size and stability in serum. It showed a significantly lower hemoglobin release than SU5416 dissolved in a Cremophor EL-containing solvent. Compared with peptide-unmodified liposomal SU5416, the APRPG-modified liposomal SU5416 significantly suppressed tumor growth and with no remarkable side effects. Thus, targeted delivery of antiangiogenic drugs with tumor vasculature-targeted liposomes may be useful for antiangiogenic cancer therapy.