The anticancer properties of iron core–gold shell nanoparticles in colorectal cancer cells

Ya-Na Wu,¹ Ping-Ching Wu,¹ Li-Xing Yang,¹ Kyle R Ratinac,² Pall Thordarson,⁴ Kristina A Jahn,² Dong-Hwang Chen,³ Dar-Bin Shieh,^1,5,6 Filip Braet<sup>2,7

1</sup>Institute of Oral Medicine and Department of Stomatology, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan; ²Australian Centre for Microscopy and Microanalysis, University of Sydney, Sydney, NSW, Australia; ³Department of Chemical Engineering, National Cheng Kung University, Tainan, Taiwan; ⁴School of Chemistry, University of New South Wales, Sydney, NSW, Australia; ⁵Center for Micro/Nano Science and Technology, National Cheng Kung University, Tainan, Taiwan; ⁶Advanced Optoelectronic Technology Center, National Cheng Kung University, Tainan, Taiwan; ⁷School of Medical Sciences (Discipline of Anatomy and Histology), The Bosch Institute, University of Sydney, Sydney, NSW, Australia

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.

Keywords: cancer therapy, Fe, gold-coated iron, nanoparticles, differential cytotoxicity