Intracellular targeting therapy of cisplatin‐encapsulated transferrin‐polyethylene glycol liposome on peritoneal dissemination of gastric cancer
Year: 2002
Type: article
Abstract: 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 reverse-phase evaporation followed by extrusion. Electron microscopic studies revealed that Tf-PEG liposomes were internalized into tumor cells by receptor-mediated endocytosis. To examine the biodistribution of each liposome and cisplatin level, nude mice were inoculated i.p. with 10(7) MKN45P human gastric tumor cells. On the fourth day after tumor inoculation, (3)H-CHE-labeled and cisplatin-encapsulated Tf-PEG, PEG or bare liposome were inoculated i.p. The Tf-PEG liposome-administered group maintained high liposome and cisplatin levels in ascites and showed a prolonged residence time in the peripheral circulation. Uptake of Tf-PEG liposomes into the liver and spleen was significantly lower than that of bare liposomes. Uptake of Tf-PEG liposomes in disseminated tumor cells of ascites and the greater omentum was significantly higher than that of PEG or bare liposomes and a significant increase in cisplatin levels was observed in these tumor cells. Mice receiving Tf-PEG liposomes 1 and 4 days after the day of tumor inoculation showed significantly higher survival rates compared with those receiving PEG liposomes without Tf, bare liposomes or free cisplatin solution. These results suggest that cisplatin-encapsulated Tf-PEG liposomes may be useful as a new intracellular targeting carrier for treatment of gastric cancer with peritoneal dissemination.
Source: International Journal of Cancer
DOI: 10.1002/ijc.10242
Authors: Hisae Iinuma, Kazuo Maruyama, Kota Okinaga, Katsunori Sasaki, Toshiyuki Sekine, Osamu Ishida, Naoko Ogiwara, Kohei Johkura, Yutaka Yonemura
Institutions: Teikyo University, Shinshu University, Kanazawa University
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: bronze
OpenAlex ID: W1970038366