Secondary cytotoxicity mediated by alveolar macrophages: A contribution to the total efficacy of nanoparticles in lung cancer therapy?
Secondary cytotoxicity mediated by alveolar macrophages: A contribution to the total efficacy of nanoparticles in lung cancer therapy?
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DOI：
10.1016/j.ejpb.2010.05.002
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发表时间：
2010-09-01
影响因子：
4.9
通讯作者：
Loebenberg, Raimar
中科院分区：
文献类型：
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作者：
Al-Hallak, Kamal M. H. D.;Azarmi, Shirzad;Loebenberg, Raimar
使用可吸入纳米颗粒（NPs）的肺癌局部治疗是一种新兴且有前途的治疗选择。本研究的目的是研究聚氰基丙烯酸异丁酯（BIPCA）纳米粒对肺泡巨噬细胞的激活作用以及这种激活对H460肺癌细胞的影响。使用甲基噻唑基二苯基-溴化四唑（MTT）测定来确定主要细胞毒性，即，负载阿霉素（DOX）的NP对两种细胞系的立即和直接细胞毒性。然后使用不同处理的EC 50浓度处理巨噬细胞，并在双室系统中与H460肺癌细胞共培养。这些处理包括DOX溶液、空白NPs和DOX负载的NPs。结果显示，暴露于空白或DOX负载的NPs的肺泡巨噬细胞在8和24 h后显示出对癌细胞的细胞毒性;这种行为在幼稚巨噬细胞或用DOX溶液处理的巨噬细胞中不表达。样品分析表明，巨噬细胞具有释放先前被吞噬的NPs片段的能力。进一步的研究表明，NPs可诱导单核细胞趋化蛋白-1（MCP-1）、巨噬细胞炎性蛋白-1（MIP-1）、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）等Th 1细胞因子分泌增加，这可能是NPs对H460肿瘤细胞产生继发性杀伤作用的原因。由巨噬细胞介导的次级细胞毒性可能补充NP对癌细胞的直接细胞毒性作用。(C)2010 Elsevier B. V.保留所有权利。
Local treatment of lung cancer using inhalable nanoparticles (NPs) is an emerging and promising treatment option. The aim of this study was to investigate the activation of alveolar macrophages by poly (isobutyl cyanoacrylate) (BIPCA) NPs and the consequences of this activation on H460 lung cancer cells. A methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was used to determine the primary cytotoxicity, that is, the immediate and direct cytotoxicity of doxorubicin (DOX)-loaded NPs on both cell lines. Macrophages were then treated using EC50 concentrations of different treatments and co-cultured in a two-compartment system with H460 lung cancer cells. These treatments included DOX solution, blank NPs, and DOX-loaded NPs.The results showed that alveolar macrophages exposed to blank or DOX-loaded NPs showed cytotoxicity against cancer cells after 8 and 24 h; this behavior was not expressed by naive macrophages or macrophages treated with DOX solution.Sample analysis indicated that macrophages have the ability to release back fragments of NPs that were previously phagocytized. Further investigations showed that NPs can induce an increase in the excretion of Th1 cytokines namely, monocytes chemoattractant protein-1 (MCP-1), macrophages inflammatory protein (MIP-1), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma).The Th1 cytokines released by the alveolar macrophages might explain the significant secondary cytotoxicity effect on H460 cancer cells. Secondary cytotoxicity mediated by macrophages might compliment the direct cytotoxic effect that NPs have on cancer cells. (C) 2010 Elsevier B.V. All rights reserved.