Antitumor effect of lipopolysaccharide by pulmonary inhalation combined with chemotherapeutic agent

R. Suzuki1, K. Hirota1, 2, Y. Ohishi1, H. Taniguchi1, H. Inagawa2, C. Kohchi2, G-I. Soma2, H. Terada1, 2

1Faculty of Pharmaceutical Sciences and 2Center for Physical Pharmaceutics, Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan  


Macrophage cells are classified into two subsets: the killer macrophages (M1 MΦs) and healer macrophages (M2 MΦs). M1 MΦs effectively attack cancer cells and generate cytokines. In contrast, M2 MΦs promote development of tumor cells due to angiogenesis. Hence, it is expected that M1 MΦs are effective for the therapy of cancer. Characteristic response of M1 MΦs is induced by a classical MΦ activating agent, such as lipopolysaccharide (LPS). However, LPS, administered intravenously, activates MΦs strongly causing inflammation in the whole body, leading to serious side effects. To achieve the high antitumor effect of LPS in addition to minimization of its side effects, we examined the effects of LPS on the lung cancer by its delivery to the lung. Such a pulmonary inhalation will enable LPS to be delivered directly to the alveolar MΦs. In addition, based on the assumption that pulmonary inhalation of LPS combined with the alkylating agent cyclophosphamide (CPA) will exert more significant antitumor effect due to induction of tumor necrosis factor-α (TNF-α), we examined the effect of CPA on the action of LPS.  

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