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A Carbohydrate Recognition–Based Drug Delivery and Controlled Release System using Intraperitoneal Macrophages as a Cellular Vehicle

¹ Division of Oncological Pathology, Aichi Cancer Center Research Institute; ² Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan; ³ Department of Applied Biochemistry and The Institute of Glycotechnology, Tokai University, Kanagawa, Japan; and ⁴ Department of Biological Chemistry, College of Bioscience and Biotechnology, Chubu University, Kasugai-shi, Japan

Requests for reprints: Naoya Kojima, Department of Applied Biochemistry, Tokai University, 1117 Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan. Phone: 81-463-58-1211; Fax: 81-463-50-2012; E-mail: naoyaki{at}keyaki.cc.u-tokai.ac.jp.

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°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. (Cancer Res 2006; 66(17): 8740-8)

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