RRC ID 42748
著者 Ikehara Y, Niwa T, Biao L, Ikehara SK, Ohashi N, Kobayashi T, Shimizu Y, Kojima N, Nakanishi H.
タイトル A carbohydrate recognition-based drug delivery and controlled release system using intraperitoneal macrophages as a cellular vehicle.
ジャーナル Cancer Res
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.
巻・号 66(17)
ページ 8740-8
公開日 2006-9-1
DOI 10.1158/0008-5472.CAN-06-0470
PII 66/17/8740
PMID 16951190
MeSH Animals Carbohydrates Delayed-Action Preparations / pharmacokinetics* Delayed-Action Preparations / pharmacology Female Fluorouracil / analogs & derivatives Fluorouracil / pharmacokinetics Fluorouracil / therapeutic use Genes, Reporter Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Humans Immunohistochemistry Liposomes / pharmacokinetics Macrophages, Peritoneal / drug effects Macrophages, Peritoneal / physiology* Mice Mice, Inbred C57BL Mice, Nude Stomach Neoplasms / drug therapy* Stomach Neoplasms / pathology Transplantation, Heterologous
IF 9.727
引用数 101
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 GCIY(RCB0555)