title: A carbohydrate recognition-based drug delivery and controlled release system using intraperitoneal macrophages as a cellular vehicle.
abstract: 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.
authors.affiliation: Division of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Ikehara
authors.forename: Toru
authors.initials: T
authors.lastname: Niwa
authors.forename: Le
authors.initials: L
authors.lastname: Biao
authors.forename: Sanae Kabata
authors.initials: SK
authors.lastname: Ikehara
authors.forename: Norifumi
authors.initials: N
authors.lastname: Ohashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Naoya
authors.initials: N
authors.lastname: Kojima
authors.forename: Hayao
authors.initials: H
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D002241:Carbohydrates; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008081:Liposomes / Q000493:pharmacokinetics; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014183:Transplantation, Heterologous
chemical_list: D002241:Carbohydrates; D003692:Delayed-Action Preparations; D008081:Liposomes; D049452:Green Fluorescent Proteins; D005472:Fluorouracil