Abstract
BackgroundNanocarriers 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.ResultsMRC 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.ConclusionMRC 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.
Highlights
Nanocarriers have the potential to improve the therapeutic index of cur‐ rently available drugs by increasing drug efficacy, lowering drug toxicity and achieving steady-state therapeutic levels of drugs over an extended period
While Maghemite nanoparticles associated with rhodium citrate (MRC) induced cytotoxicity in MDA-MB-231 in a time-dependent manner, progressively decreasing the required dose for significant reduction in cell viability after 48 and 72 h, MCF-7 appears to recover its viability from 48 h of exposure (Fig. 1b, c)
The MRC cytotoxicity effect was dependent on concentration and time of exposure in MDA-MB-23 cells, whereas prolonged exposure was not effective in MCF-7 cells
Summary
Nanocarriers have the potential to improve the therapeutic index of cur‐ rently 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. Cancer cell targeting would benefit greatly from highly specific and localized drug delivery In this context, iron oxide nanoparticles hold great promise as diagnostic and therapeutic agents in oncology. Iron oxide nanoparticles hold great promise as diagnostic and therapeutic agents in oncology Their intrinsic physical properties are interesting for simultaneous drug delivery, molecular imaging and applications such as localized hyperthermia (Bender et al 2018; Iv et al 2015). Maghemite nanoparticles associated with rhodium citrate (MRC) have showed colloidal stability and antitumor activity in breast cancer cells (Carneiro et al 2011; Peixoto et al 2015; Chaves et al 2015; da Silva Nunes et al 2013; Rocha et al 2017)
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