Cancer-cell-specific cytotoxicity of non-oxidized iron elements in iron core-gold shell NPs
ABSTRACT Gold-coated iron nanoparticles (NPs) selectively and significantly (P <0.0001) inhibit proliferation of oral- and colorectal-cancer cells in vitro at doses as low as 5 μg/mL, but have little adverse effect on normal healthy control cells. The particle treatment caused delay in cell-cycle progression, especially in the S-phase. There was no significant difference in the NP uptake between cancer and control cells, and cytotoxicity resulted primarily from the iron core, before oxidation, rather than from the Fe ions released from the core. In contrast with magnetic NPs that usually serve as drug carriers, diagnostic probes or hyperthermia media, the iron, before oxidation, in the NPs selectively suppressed cancer cell growth and left healthy control cells unaffected in vitro and in vivo. This novel nanomaterial holds great promise as a therapeutic tool in nanomedicine. FROM THE CLINICAL EDITOR: Gold-coated iron nanoparticles (NPs) selectively suppressed squamous cell carcinoma (SCC) and colorectal cancer (CRC) cell growth, but left healthy control cells unaffected both in vitro and in vivo. The particles were equally uptaken by all cells, but delayed cell progression only for cancer cells. The origin is related to the iron core: neither iron ions nor the oxidized NPs have the same outcome.
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ABSTRACT: Previously, iron core-gold shell nanoparticles (Fe@Au) have been shown to possess cancer-preferential cytotoxicity in oral and colorectal cancer (CRC) cells. However, CRC cell lines are less sensitive to Fe@Au treatment when compared with oral cancer cell lines. In this research, Fe@Au are found to decrease the cell viability of CRC cell lines, including Caco-2, HT-29, and SW480, through growth inhibition rather than the induction of cell death. The cytotoxicity induced by Fe@Au in CRC cells uses different subcellular pathways to the mitochondria-mediated autophagy found in Fe@Au-treated oral cancer cells, OECM1. Interestingly, the Caco-2 cell line shows a similar response to OECM1 cells and is thus more sensitive to Fe@Au treatment than the other CRC cell lines studied. We have investigated the underlying cell resistance mechanisms of Fe@Au-treated CRC cells. The resistance of CRC cells to Fe@Au does not result from the total amount of Fe@Au internalized. Instead, the different amounts of Fe and Au internalized appear to determine the different response to treatment with Fe-only nanoparticles in Fe@Au-resistant CRC cells compared with the Fe@Au-sensitive OECM1 cells. The only moderately cytotoxic effect of Fe@Au nanoparticles on CRC cells, when compared to the highly sensitive OECM1 cells, appears to arise from the CRC cells' relative insensitivity to Fe, as is demonstrated by our Fe-only treatments. This is a surprising outcome, given that Fe has thus far been considered to be the "active" component of Fe@Au nanoparticles. Instead, we have found that the Au coatings, previously considered only as a passivating coating to protect the Fe cores from oxidation, significantly enhance the cytotoxicity of Fe@Au in certain CRC cells. Therefore, we conclude that both the Fe and Au in these core-shell nanoparticles are essential for the anticancer properties observed in CRC cells.International Journal of Nanomedicine 09/2013; 8:3321-31. DOI:10.2147/IJN.S47742 · 4.20 Impact Factor
- Chemical Reviews 06/2014; 114(15). DOI:10.1021/cr400372p · 45.66 Impact Factor
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ABSTRACT: Autophagy has attracted a great deal of research interest in tumor therapy in recent years. An attempt was made in this direction and now we report that iron oxide NPs synthesized by us selectively induce autophagy in cancer cells (A549) and not in normal cells (IMR-90). It was also noteworthy that autophagy correlated with ROS production as well as mitochondrial damage. Protection of NAC against ROS clearly suggested the implication of ROS in hyper-activation of autophagy and cell death. Pre-treatment of cancer cells with 3-MA also exhibited protection against autophagy and promote cellular viability. Results also showed involvement of classical mTOR pathway in autophagy induction by iron oxide NPs in A549 cells. Our results had shown that bare iron oxide NPs are significantly cytotoxic to human cancer cells (A549) but not to the normal human lung fibroblast cells (IMR-90).In other words our nanoparticles selectively kill cancerous cells. It is encouraging to conclude that iron oxide NPs bear the potential of its applications in biomedicine, such as tumor therapy specifically by inducing autophagy mediated cell death of cancer cells.Biomaterials 11/2011; 33(5):1477-88. DOI:10.1016/j.biomaterials.2011.10.080 · 8.31 Impact Factor