Nanoparticle-Mediated Delivery of Anticancer Agents to Tumor Angiogenic Vessels

Abstract

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.

Nanoparticle-Mediated Drug Delivery System for Cardiovascular Disease

“…2) This phenomenon is referred to as enhanced permeability and retention (EPR) effects of nano-DDS. 27) Recognition and incorporation by the mononuclear phagocyte system (MPS, also called the reticuloendothelial system), namely neutrophils, monocytes, and macrophages in the blood, liver, spleen, and lymph nodes is also a common physiological behavior for nano-DDS, which may affect the blood circulating time and tissue/cell distribution. [28][29][30][31] One of the first clinically approved nano-scale DDS therapies was a liposomal formulation of doxorubicin, a cytotoxic drug used for cancer chemotherapy.…”

Innovations in Liposomal DDS Technology and Its Application for the Treatment of Various Diseases

“…[23][24][25][26] In this type of therapy, anticancer drugs are expected to be efficiently delivered to angiogenic endothelial cells, since such drugs contained in liposomes firstly meet blood vessels after injec- Naoto Oku tion of them into bloodstream and, thus, easily interact with them. 27,28) Lipid composition and characteristics of liposomes used for ANET and other studies described in the review are shown in Table 1. Recently, Hansen et al determined the distribution of copper-64 encapsulated in PEGylated liposomes and evaluated the EPR effect in 11 canine cancer patients with spontaneous solid tumors.…”

Anti-inflammatory Nanoparticle for Prevention of Atherosclerotic Vascular Diseases

“…In tumor tissues, immature lymphatic vessels retard elimination of nanoparticles. These effects are known as enhanced permeability and retention effects 22,23) . Surface modification with polyethylene glycol (PEG) prevents entrapment of nano particles by the reticuloendothelial system due to its hydrophilic property.…”