For the purpose of
cancer anti-neovascular
therapy (ANET), we previously isolated 5-mer
peptide Ala-Pro-Arg-Pro-Gly (APRPG) that specifically bound to the
tumor angiogenic site and observed that APRPG-modified
liposomes encapsulating
adriamycin were effective for the suppression of
tumor in
tumor-bearing mice. Since
polyethylene glycol (PEG) modification of
liposomes endows them with a future of long circulation, we modified
liposomes with PEG and APRPG-conjugated distearoylphosphatidylethanolamine (
DSPE-PEG-APRPG) and examined the applicability of the
liposomes on ANET.
Liposomes containing
DSPE-PEG-APRPG not only specifically bound to
vascular endothelial growth factor-stimulated human umbilical vein endothelial cells in vitro, but also showed long-circulating characteristic and enhanced accumulation in
tumor in vivo. Furthermore,
adriamycin-encapsulated
liposomes modified with APRPG-PEG caused more efficient
tumor growth suppression than
adriamycin-encapsulated
liposomes modified with PEG alone in Colon 26 NL-17
carcinoma-bearing mice, despite not so much different accumulation of both
liposomes in the
tumor. These data suggest that
tumor neovasculature-targeted long-circulating
liposomes encapsulating anti-
cancer drugs effectively eradicate cancerous cells through damaging of angiogenic endothelial cells. ANET promises no drug resistance and is expected to be effective against essentially any kind of solid
tumors. The present results demonstrate the beneficial usage of APRPG-PEG for the active-targeting of
drug carriers to angiogenic site in the novel modality of
tumor treatment, namely ANET.