Peritoneal dissemination in gastric cancer is a common fatal clinical condition with few effective therapies available. We studied the therapeutic effect of a tumor-targeting drug delivery system that uses cisplatin-encapsulated and Tf-conjugated PEG liposomes (Tf-PEG liposomes) in nude mice with peritoneal dissemination of human gastric cancer cells. Small unilamellar Tf-PEG, PEG or DSPC/CH liposomes (bare liposomes) encapsulating cisplatin were prepared by reversephase evaporation followed by extrusion. Electron microscopic studies revealed that Tf-PEG liposomes were internal-
Key words: liposome; targeting; transferrin; peritoneal dissemination; gastric cancerPeritoneal dissemination is the most frequent noncurative factor and the most common type of recurrence after curative surgery in patients with gastric cancer. 1 Control of this metastasis is one of the most important challenges in treating gastric cancer. There have been few reports of effective treatment for peritoneal dissemination in patients with gastric cancer. 2,3 As a clinical locoregional chemotherapy, various anticancer drugs in solution form have been administered i.p. to expose the drug directly to peritoneal tumor cells. 4 However, small water-soluble molecules, such as cisplatin or mitomycin C, are absorbed easily through the large peritoneal surface into the circulating blood. It is difficult to maintain a high drug concentration for a long time in the peritoneal cavity. 5,6 Therefore, i.p. administration of anticancer drugs in solution form does not always produce the desired effect.Liposomes, known to be drug carriers, have various advantages. 7,8 First, they encapsulate various drugs such as water-soluble, lipid-soluble or high m.w. substances and release them in a sustained manner. Second, the antigenicity and toxicity of liposomes are very low because they consist of lipid, which is a natural component of organisms. Third, the biodistribution of liposomes can be controlled by the size or lipid component. Fourth, various materials, such as antibodies or chemical compounds, can modify the surfaces of liposomes. However, the therapeutic application of liposomes has been limited by their rapid clearance from the bloodstream and by their uptake by the RES. Recent efforts have been made to reformulate the liposome composition, to reduce its affinity to the RES. Liposomes modified with amphipathic PEG are not readily taken up by macrophages in the RES and, hence, stay in the circulation for a relatively long time. 9 -14 To increase the therapeutic effect and decrease side effects, tumor-specific targeting therapy has been advocated. Intracellular targeting using iron-saturated Tf as a ligand for receptor-mediated endocytosis has attracted attention. Tf is a glycoprotein that transports ferric ions in the body and the Tf receptor is internalized into cells by endocytosis through the binding of Tf. This receptormediated endocytosis is a normal physiologic process by which iron is delivered to cells. [15][16][17] Also, the Tf receptor concen...