Nanocarriers have the potential to improve the therapeutic index of currently available drugs by increasing drug efficacy, lowering drug toxicity and achieving steady-state therapeutic levels of drugs over an extended period. The association of maghemite nanoparticles (NPs) with rhodium citrate (forming the complex hereafter referred to as MRC) has the potential to increase the specificity of the cytotoxic action of the latter compound, since this nanocomposite can be guided or transported to a target by the use of an external magnetic field. However, the behavior of these nanoparticles for an extended time of exposure to breast cancer cells has not yet been explored, and nor has MRC cytotoxicity comparison in different cell lines been performed until now. In this work, the effects of MRC NPs on these cells were analyzed for up to 72 h of exposure, and we focused on comparing NPs’ therapeutic effectiveness in different cell lines to elect the most responsive model, while elucidating the underlying action mechanism. MRC complexes exhibited broad cytotoxicity on human tumor cells, mainly in the first 24 h. However, while MRC induced cytotoxicity in MDA-MB-231 in a time-dependent manner, progressively decreasing the required dose for significant reduction in cell viability at 48 and 72 h, MCF-7 appears to recover its viability after 48 h of exposure. The recovery of MCF-7 is possibly explained by a resistance mechanism mediated by PGP (P-glycoprotein) proteins, which increase in these cells after MRC treatment. Remaining viable tumor metastatic cells had the migration capacity reduced after treatment with MRC (24 h). Moreover, MRC treatment induced S phase arrest of the cell cycle. MRC act at the nucleus, inhibiting DNA synthesis and proliferation and inducing cell death. These effects were verified in both tumor lines, but MDA-MB-231 cells seem to be more responsive to the effects of NPs. In addition, NPs may also disrupt the metastatic activity of remaining cells, by reducing their migratory capacity. Our results suggest that MRC nanoparticles are a promising nanomaterial that can provide a convenient route for tumor targeting and treatment, mainly in metastatic cells.

中文翻译：

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柠檬酸铑相关的氧化铁纳米粒子对转移性和非转移性乳腺癌细胞作用的比较

纳米载体具有通过增加药物功效，降低药物毒性并在延长的时期内达到稳态药物治疗水平来改善当前可用药物的治疗指数的潜力。磁赤铁矿纳米粒子（NPs）与柠檬酸铑的结合（形成复合物，以下称为MRC）具有增加后一种化合物的细胞毒作用特异性的潜力，因为该纳米复合物可以被纳米复合物引导或转运至靶标。使用外部磁场。然而，尚未研究这些纳米粒子在延长的乳腺癌细胞暴露时间中的行为，并且至今还没有在不同细胞系中进行MRC细胞毒性比较。在这项工作中，分析了MRC NP对这些细胞长达72小时的暴露的影响，我们重点比较了NP在不同细胞系中的治疗效果，以选择反应最强的模型，同时阐明了潜在的作用机制。MRC复合物对人肿瘤细胞表现出广泛的细胞毒性，主要在最初的24小时内。但是，虽然MRC以时间依赖性方式诱导了MDA-MB-231的细胞毒性，但逐渐降低了48和72 h细胞活力显着降低所需的剂量，而MCF-7暴露48 h后似乎恢复了其活力。MCF-7的恢复可能是由PGP（P-糖蛋白）蛋白介导的抗性机制解释的，在MRC处理后这些细胞中的抗性机制增加。剩余的存活肿瘤转移细胞经MRC处理（24小时）后迁移能力降低。而且，MRC处理诱导细胞周期的S期停滞。MRC作用于细胞核，抑制DNA合成和增殖并诱导细胞死亡。在两种肿瘤细胞系中均已证实了这些作用，但MDA-MB-231细胞似乎对NP的作用更敏感。另外，NP还可以通过降低其迁移能力来破坏其余细胞的转移活性。我们的结果表明，MRC纳米颗粒是一种有前途的纳米材料，可以为肿瘤靶向和治疗（主要是在转移细胞中）提供便利的途径。