title: The anticancer properties of iron core-gold shell nanoparticles in colorectal cancer cells.
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.
authors.affiliation: Institute of Oral Medicine and Department of Stomatology, National Cheng Kung University Hospital, College of Medicine, Tainan, Taiwan.
authors.forename: Ya-Na
authors.initials: YN
authors.lastname: Wu
authors.forename: Ping-Ching
authors.initials: PC
authors.lastname: Wu
authors.forename: Li-Xing
authors.initials: LX
authors.lastname: Yang
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Ratinac
authors.forename: Pall
authors.initials: P
authors.lastname: Thordarson
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Jahn
authors.forename: Dong-Hwang
authors.initials: DH
authors.lastname: Chen
authors.forename: Dar-Bin
authors.initials: DB
authors.lastname: Shieh
authors.forename: Filip
authors.initials: F
authors.lastname: Braet
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D006046:Gold / Q000627:therapeutic use*; D019073:HT29 Cells; D006801:Humans; D007501:Iron / Q000627:therapeutic use*; D053768:Metal Nanoparticles / Q000627:therapeutic use* / Q000648:ultrastructure*; D010316:Particle Size
chemical_list: D006046:Gold; D007501:Iron
keywords: Fe; cancer therapy; differential cytotoxicity; gold-coated iron; nanoparticles
references.citation: Biomaterials. 2011 Jul;32(20):4565-73
references.pmid: 21458061
references.citation: J Biol Chem. 2000 Jun 30;275(26):19906-12
references.pmid: 10747949
references.citation: Mol Imaging. 2011 Oct;10(5):340-58
references.pmid: 21521554
references.citation: Chemistry. 2007;13(14):3878-85
references.pmid: 17300114
references.citation: Invest Ophthalmol Vis Sci. 2012 Jul 24;53(8):4874-80
references.pmid: 22661476
references.citation: Chem Res Toxicol. 2008 Sep;21(9):1726-32
references.pmid: 18710264
references.citation: Nano Rev. 2010;1:
references.pmid: 22110864
references.citation: Langmuir. 2007 Aug 14;23(17):9050-6
references.pmid: 17629315
references.citation: Part Fibre Toxicol. 2009 Jun 22;6:18
references.pmid: 19545423
references.citation: Biomaterials. 2005 Dec;26(34):7183-91
references.pmid: 15964622
references.citation: Cytometry A. 2010 Oct;77(10):933-9
references.pmid: 21290467
references.citation: Biomaterials. 2005 Jun;26(18):3995-4021
references.pmid: 15626447
references.citation: Int J Nanomedicine. 2013;8:1825-34
references.pmid: 23674894
references.citation: Curr Cancer Drug Targets. 2011 Feb;11(2):184-9
references.pmid: 21158723
references.citation: Eur Radiol. 2003 Jun;13(6):1266-76
references.pmid: 12764641
references.citation: Cancer Immunol Immunother. 2006 Mar;55(3):320-8
references.pmid: 16133113
references.citation: Toxicol In Vitro. 2009 Oct;23(7):1406-11
references.pmid: 19607906
references.citation: Nanotoxicology. 2012 Jun;6(4):440-52
references.pmid: 21635174
references.citation: J Am Chem Soc. 2010 Sep 29;132(38):13270-8
references.pmid: 20572667
references.citation: Nano Lett. 2006 Jun;6(6):1261-8
references.pmid: 16771591
references.citation: Nanomedicine. 2011 Aug;7(4):420-7
references.pmid: 21272668
references.citation: Mol Pharm. 2008 Mar-Apr;5(2):316-27
references.pmid: 18217714
references.citation: J Pharmacol Toxicol Methods. 1997 Jun;37(4):215-28
references.pmid: 9279777
references.citation: J Nanosci Nanotechnol. 2010 Sep;10(9):5527-39
references.pmid: 21133071
references.citation: Int J Biochem Cell Biol. 2005 Sep;37(9):1768-73
references.pmid: 16009323
references.citation: Bioorg Med Chem. 2006 Jan 1;14(1):263-72
references.pmid: 16213738