期刊
JOURNAL OF CONTROLLED RELEASE
卷 68, 期 2, 页码 283-289出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S0168-3659(00)00269-8
关键词
doxorubicin; M5076 cells; nanoparticle; J774.A1; coculture
Doxorubicin-loaded PACA nanoparticles have been shown to be more efficient than free drug in mice bearing hepatic metastasis of the M5076 tumour. Due to the high phagocytic activity of Kupffer cells in the liver, it may be that these cells played a role of drug reservoir after nanoparticle phagocytosis. Therefore, the objective of this study was to assess the role of macrophages in mediating the cytotoxicity of doxorubicin-loaded nanoparticles on M5076 cells. The growth inhibition of tumour cells was evaluated in two ways: firstly, the cells were incubated in a coculture system consisting of special wells with two compartments separated by a porous membrane. M5076 cells were seeded into the lower compartment and the macrophages J774.A1 were introduced into the upper part. The macrophages were activated or not by IFN-gamma. The drug preparations were added only in the macrophage insert. Secondly, growth inhibition was also assessed in the conventional way, i.e. in direct contact with the tumour cells to serve as a reference. After direct contact, free doxorubicin (Dox) and doxorubicin-loaded nanoparticles (NP-Dox) had the same efficacy against M5076 cell growth. The coculture experiments led to a 5-fold increase in the IC50 for both Dox and NP-Dox. The activation of macrophages by IFN-gamma in coculture significantly decreased the IC50 values. In conclusion, after phagocytosis of doxorubicin-loaded nanoparticles, J774.A1 cells were able to release active drug, allowing it to exert its cytotoxicity against M5076 cells. Drug efficacy was potentiated by the activation of macrophages releasing cytotoxic factors such as NO, which resulted in increased tumour cell death. Thereby, the coculture system permitted us to investigate the macrophage-mediated cytotoxicity of colloidal carriers loaded with an anticancer drug, which is of great interest when further i.v. administration is envisaged. (C) 2000 Elsevier Science B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据