title: Novel ZnO:Ag nanocomposites induce significant oxidative stress in human fibroblast malignant melanoma (Ht144) cells.
abstract: The use of photoactive nanoparticles (NPs) such as zinc oxide (ZnO) and its nanocomposites has become a promising anticancer strategy. However, ZnO has a low photocatalytic decomposition rate and the incorporation of metal ions such as silver (Ag) improves their activity. Here different formulations of ZnO:Ag (1, 3, 5, 10, 20 and 30% Ag) were synthesized by a simple co-precipitation method and characterized by powder X-ray diffraction, scanning electron microscopy, Rutherford back scattering and diffuse reflectance spectroscopy for their structure, morphology, composition and optical band gap. The NPs were investigated with regard to their different photocatalytic cytotoxic effects in human malignant melanoma (HT144) and normal (HCEC) cells. The ZnO:Ag nanocomposites killed cancer cells more efficiently than normal cells under daylight exposure. Nanocomposites having higher Ag content (10, 20 and 30%) were more toxic compared to low Ag content (1, 3 and 5%). For HT144, under daylight exposure, the IC50 values were ZnO:Ag (10%): 23.37 μg/mL, ZnO:Ag (20%): 19.95 μg/mL, and ZnO:Ag (30%): 15.78 μg/mL. ZnO:Ag (30%) was toxic to HT144 (IC50: 23.34 μg/mL) in dark as well. The three nanocomposites were further analyzed with regard to their ability to generate reactive oxygen species (ROS) and induce lipid peroxidation. The particles led to an increase in levels of ROS at cytotoxic concentrations, but only HT144 showed strongly induced MDA level. Finally, NPs were investigated for the ROS species they generated in vitro. A highly significant increase of (1)O2 in the samples exposed to daylight was observed. Hydroxyl radical species, HO(•), were also generated to a lesser extent. Thus, the incorporation of Ag into ZnO NPs significantly improves their photo-oxidation capabilities. ZnO:Ag nanocomposites could provide a new therapeutic option to selectively target cancer cells.
authors.affiliation: Nanosciences and Catalysis Division, National Centre for Physics, Quaid-i-Azam University campus, Islamabad, Pakistan ; Department of Chemistry, University of Hazara, Mansehra, KPK, Pakistan.
authors.forename: Syeda
authors.initials: S
authors.lastname: Arooj
authors.affiliation: Nanosciences and Catalysis Division, National Centre for Physics, Quaid-i-Azam University campus, Islamabad, Pakistan.
authors.forename: Samina
authors.initials: S
authors.lastname: Nazir
authors.affiliation: Department of Biotechnology, Faculty of Biological Science, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Akhtar
authors.initials: A
authors.lastname: Nadhman
authors.affiliation: Institute of Biomedical and Genetic Engineering, G-9/1, Islamabad, Pakistan.
authors.forename: Nafees
authors.initials: N
authors.lastname: Ahmad
authors.affiliation: Department of Chemistry, University of Hazara, Mansehra, KPK, Pakistan.
authors.forename: Bakhtiar
authors.initials: B
authors.lastname: Muhammad
authors.affiliation: Accelerator Lab, National Centre for Physics, Quaid-i-Azam University campus, Islamabad, Pakistan.
authors.forename: Ishaq
authors.initials: I
authors.lastname: Ahmad
authors.affiliation: Institute of Biomedical and Genetic Engineering, G-9/1, Islamabad, Pakistan.
authors.forename: Kehkashan
authors.initials: K
authors.lastname: Mazhar
authors.affiliation: Institute of Biomedical and Genetic Engineering, G-9/1, Islamabad, Pakistan.
authors.forename: Rashda
authors.initials: R
authors.lastname: Abbasi
keywords: ZnO:Ag nanocomposites; cancer therapy; cytotoxicity; photo-oxidation
references.citation: J Photochem Photobiol B. 2014 Sep 5;138:99-108
references.pmid: 24911277
references.citation: Nanoscale Res Lett. 2009 Sep 16;4(12):1409-20
references.pmid: 20652105
references.citation: Int J Nanomedicine. 2012;7:845-57
references.pmid: 22393286
references.citation: Int J Oncol. 2010 Dec;37(6):1583-90
references.pmid: 21042728
references.citation: Expert Opin Drug Deliv. 2010 Sep;7(9):1063-77
references.pmid: 20716019
references.citation: Nanoscale Res Lett. 2010 Apr 16;5(6):1063-71
references.pmid: 20671778
references.citation: Acta Pharmacol Sin. 2012 Oct;33(10):1319-24
references.pmid: 22842729
references.citation: J Mater Chem B. 2013 Oct 14;1(38):5003-5013
references.pmid: 32261090
references.citation: Anal Biochem. 1979 Jun;95(2):351-8
references.pmid: 36810
references.citation: ACS Nano. 2008 Oct 28;2(10):2121-34
references.pmid: 19206459
references.citation: Nanotoxicology. 2013 Jun;7(4):402-16
references.pmid: 22394310
references.citation: Photochem Photobiol. 1999 Oct;70(4):391-475
references.pmid: 10546544
references.citation: Trends Biotechnol. 2008 Nov;26(11):612-21
references.pmid: 18804298
references.citation: Toxicol Sci. 2013 Nov;136(1):120-30
references.pmid: 23997113
references.citation: Theranostics. 2013 Mar 25;3(5):317-30
references.pmid: 23650479
references.citation: Nanotechnology. 2008 Feb 20;19(7):075104
references.pmid: 21817629
references.citation: Australas J Dermatol. 2011 Feb;52(1):1-6
references.pmid: 21332685
references.citation: Oncologist. 2006 Oct;11(9):1034-44
references.pmid: 17030646
references.citation: Cancers (Basel). 2011;3(2):2516-39
references.pmid: 23914299
references.citation: J Photochem Photobiol B. 2009 Jul 17;96(1):1-8
references.pmid: 19406659
references.citation: ACS Nano. 2011 May 24;5(5):3651-9
references.pmid: 21452822
references.citation: Langmuir. 2011 Apr 5;27(7):4020-8
references.pmid: 21401066
references.citation: J Immunol Methods. 1983 Dec 16;65(1-2):55-63
references.pmid: 6606682
references.citation: Nat Clin Pract Urol. 2009 Jan;6(1):18-30
references.pmid: 19132003
references.citation: Nanotoxicology. 2012 Jun;6(4):440-52
references.pmid: 21635174
references.citation: ACS Nano. 2013 Dec 23;7(12):10621-35
references.pmid: 24187959
references.citation: PLoS One. 2013 Jun 03;8(6):e65704
references.pmid: 23755271
references.citation: Nanomedicine. 2011 Apr;7(2):184-92
references.pmid: 21034861
references.citation: Nanomedicine. 2011 Dec;7(6):904-13
references.pmid: 21664489
references.citation: Chem Pharm Bull (Tokyo). 2012;60(7):818-24
references.pmid: 22790812
references.citation: J Mater Sci Mater Med. 2009 Jan;20(1):11-22
references.pmid: 18651111
references.citation: PLoS One. 2012;7(11):e48617
references.pmid: 23144911
references.citation: J Med Life. 2013 Mar 15;6(1):50-4
references.pmid: 23599819
references.citation: J Natl Cancer Inst. 1990 Jul 4;82(13):1107-12
references.pmid: 2359136
references.citation: Nanotechnology. 2008 Jul 23;19(29):295103
references.pmid: 18836572
references.citation: Int J Biochem Cell Biol. 2013 Aug;45(8):1849-59
references.pmid: 23764618
references.citation: FASEB J. 2005 Mar;19(3):311-30
references.pmid: 15746175
references.citation: Nanomedicine. 2014 Jan;10(1):19-34
references.pmid: 23871761