Targeted delivery of oligomannose-coated liposome to the omental micrometastasis by peritoneal macrophages from patients with gastric cancer.

We recently developed a novel drug delivery system (DDS) using oligomannose-coated liposomes (OMLs), which are effectively taken up by mouse peritoneal macrophages to carry anticancer drugs to omental milky spots known as initial metastatic sites in the peritoneal cavity in mice. However, the feasibility of the clinical application of this DDS to gastric cancer patients remains essentially unknown. In the present study, we investigated whether human peripheral blood monocytes (PBMs) and human peritoneal macrophages (PEMs) could successfully uptake OMLs and deliver them to the micrometastatic foci in the mouse omentum and resected omentum from cancer patients ex vivo. When OMLs were incubated with the PBMs from four healthy volunteers in vitro, an average 88% of CD14-positive PBMs, most of which also express CD206, took up OMLs, and this uptake was significantly inhibited by alpha-methylmannoside. In the experiment using PEMs obtained from peritoneal washes of five gastric cancer patients, the average uptake rate (63%) of OML by CD14-positive PEMs was somewhat lower than that of PBMs, but in three advanced gastric cancer patients the uptake rate of OMLs was 76% which was comparable to that of mouse PEMs. Oligomannose-coated liposome (OML)-incorporated PBMs and PEMs were successfully accumulated at the micrometastatic foci at the omentum formed after intraperitoneal injection of GFP-tagged gastric cancer cells into mice. Furthermore, OML-incorporated PBMs substantially accumulated to tumor foci in the surgically resected human omentum ex vivo. These results suggest that OMLs using human monocytes/macrophages as a cellular vehicle have the potential to target peritoneal micrometastasis in the omentum of gastric cancer patients.