Nanoparticle-mediated delivery of anticancer agents to tumor angiogenic vessels

Nanoparticle-mediated drug delivery systems targeting tumor angiogenic vessels have been studied for antineovascular cancer therapy achieved by induction of apoptosis of angiogenic endothelial cells. Nanoparticles such as liposomes are considered to accumulate in tumors due to the enhanced permeability and retention effect. The delivery efficiency of this system appears to be affected by the density of tumor angiogenic vessels regardless of modification with tumor-targeting ligands on the surface of nanoparticles. It remains a challenging problem to deliver sufficient amounts of anticancer drugs to hypovascular tumors using nanoparticles. On the other hand, the strategy of angiogenic vessel-targeting is theoretically different from that of tumor cell-targeting since target angiogenic endothelial cells face the circulating blood. In addition, this strategy is expected to cause indirect tumor regression by disrupting angiogenic vessels. In this review, our recent studies are summarized to show the actual efficacy of angiogenic vessel-targeting delivery. We have developed various angiogenic vessel-targeted liposomes and evaluated them in experimental cancer models such as drug-resistant and hypovascular tumors. Our data indicate that increased apoptosis of angiogenic endothelial cells can be achieved by the targeted liposomes encapsulating cytotoxic drugs, resulting in enhanced anticancer effects. The advantages of angiogenic vessel-targeting are discussed based on our recent findings to provide an insight into why angiogenic vessels are a promising target for advanced cancer therapy.