A carbohydrate recognition-based drug delivery and controlled release system using intraperitoneal macrophages as a cellular vehicle

• Published in: Cancer research (Chicago, Ill.) Vol. 66; no. 17; pp. 8740 - 8748
• Main Authors: IKEHARA, Yuzuru, NIWA, Toru, LE BIAO, IKEHARA, Sanae Kabata, OHASHI, Norifumi, KOBAYASHI, Takeshi, SHIMIZU, Yoshitaka, KOJIMA, Naoya, NAKANISHI, Hayao
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.09.2006
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Carbohydrates; Chemotherapy; Delayed-Action Preparations - pharmacokinetics; Delayed-Action Preparations - pharmacology; Female; Fluorouracil - analogs & derivatives; Fluorouracil - pharmacokinetics; Fluorouracil - therapeutic use; General pharmacology; Genes, Reporter; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Humans; Immunohistochemistry; Liposomes - pharmacokinetics; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - physiology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Nude; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Transplantation, Heterologous; Antineoplastic agent; Intraperitoneal administration; Controlled release form; Dosage form; Liposome; Drug carrier; Omentum; Carbohydrate; Lymphoid tissue; In vitro; Macrophage
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-06-0470

The lymphoid tissue in the omentum, at the so-called milky spots, is known as an initial place for disseminated cancer cells to develop into solid tumors. In the present study, i.p. macrophages significantly took up oligomannose-coated liposomes (OMLs) that were injected into the peritoneal cavity, and then gradually accumulated in the omentum and the other lymphoid tissues within 24 hours of i.p. injection of OMLs. When 5-fluorouracil (5-FU) was encapsulated in the OMLs, >60% of administered 5-FU accumulated in the omentum. Treatment of macrophages at 39 degrees C for 30 minutes led to the release of 5-FU from the macrophages, suggesting that controlled release from macrophages could be achieved by mild hyperthermia. We encased magnetic nanoparticles, which are known to convert electromagnetic energy to heat in the OMLs to achieve in vivo hyperthermia at the site. Using this system in a mouse i.p. metastasis model, we successfully controlled tumor development by coadministration of OML-encased 5-FU and OML-encased magnetic nanoparticles, followed by treatment with an alternating magnetic field. No apparent reduction was seen in tumor growth with the administration of OML-encased magnetic nanoparticles or OML-encased 5-FU alone. Thus, we have established the use of i.p. macrophages as a novel drug delivery system for the control of cancer metastatic to milky spots.