Abstract
Nanoparticles (NPs) are finding increasing use in food science, but the toxicity of NPs following oral exposure is not fully known. When present in food and food-related products, food components may interact with NPs and thus influence the toxicity of NPs, but relatively few studies have considered the interactions between food components and ZnO NPs. In this study, the interactions between ZnO NPs with different sizes (20 and 100 nm; uncoated) and palmitate (PA) on the toxicity of NPs to Caco-2 cells were investigated. The presence of PA altered UV-Vis spectra, hydrodynamic size, and zeta potential of ZnO NPs of both sizes, which indicated an interaction between PA and ZnO NPs. Furthermore, the interaction decreased the solubility of ZnO NPs in water and cell culture medium. Exposure to both types of ZnO NPs was associated with significantly increased cytotoxicity, lysosomal damages, and intracellular Zn accumulation but not reactive oxygen species (ROS) or release of interleukin-8 (IL-8) in Caco-2 cells. The presence of 100 μM PA did not significantly affect all of these endpoints, and ANOVA analysis indicated no interaction between concentrations of ZnO NPs and the presence of PA. It is concluded that PA as a saturated fatty acid may influence the colloidal stability of ZnO NPs but did not affect the toxicity of ZnO NPs to Caco-2 cells.
This is a preview of subscription content,
to check access.








Similar content being viewed by others
References
Abbott Chalew TE, Schwab KJ (2013) Toxicity of commercially available engineered nanoparticles to Caco-2 and SW480 human intestinal epithelial cells. Cell Biol Toxicol 29:101–116
Buerki-Thurnherr T, Xiao L, Diener L, Arslan O, Hirsch C, Maeder-Althaus X, Grieder K, Wampfler B, Mathur S, Wick P, Krug HF (2013) In vitro mechanistic study towards a better understanding of ZnO nanoparticle toxicity. Nanotoxicology 7:402–416
Bumbudsanpharoke N, Ko S (2015) Nano-food packaging: an overview of market, migration research, and safety regulations. J Food Sci 80:R910–R923
Cao Y, Jantzen K, Gouveia AC, Skovmand A, Roursgaard M, Loft S, Moller P (2015a) Automobile diesel exhaust particles induce lipid droplet formation in macrophages in vitro. Environ Toxicol Pharmacol 40:164–171
Cao Y, Li J, Liu F, Li X, Jiang Q, Cheng S, Gu Y (2016a) Consideration of interaction between nanoparticles and food components for the safety assessment of nanoparticles following oral exposure: a review. Environ Toxicol Pharmacol 46:206–210
Cao Y, Roursgaard M, Jacobsen NR, Moller P, Loft S (2016b) Monocyte adhesion induced by multi-walled carbon nanotubes and palmitic acid in endothelial cells and alveolar-endothelial co-cultures. Nanotoxicology 10:235–244
Cao Y, Roursgaard M, Kermanizadeh A, Loft S, Moller P (2015b) Synergistic effects of zinc oxide nanoparticles and fatty acids on toxicity to caco-2 cells. Int J Toxicol 34:67–76
Chen G, Shen Y, Li X, Jiang Q, Cheng S, Gu Y, Liu L, Cao Y (2017) The endoplasmic reticulum stress inducer thapsigargin enhances the toxicity of ZnO nanoparticles to macrophages and macrophage-endothelial co-culture. Environ Toxicol Pharmacol 50:103–110
Chen Z, Wang Y, Zhuo L, Chen S, Zhao L, Chen T, Li Y, Zhang W, Gao X, Li P, Wang H, Jia G (2015) Interaction of titanium dioxide nanoparticles with glucose on young rats after oral administration. Nanomedicine 11:1633–1642
Choi SJ, Choy JH (2014) Biokinetics of zinc oxide nanoparticles: toxicokinetics, biological fates, and protein interaction. Int J Nanomedicine 9(Suppl 2):261–269
De Angelis I, Barone F, Zijno A, Bizzarri L, Russo MT, Pozzi R, Franchini F, Giudetti G, Uboldi C, Ponti J, Rossi F, De BB (2013) Comparative study of ZnO and TiO(2) nanoparticles: physicochemical characterisation and toxicological effects on human colon carcinoma cells. Nanotoxicology 7:1361–1372
Docter D, Westmeier D, Markiewicz M, Stolte S, Knauer SK, Stauber RH (2015) The nanoparticle biomolecule corona: lessons learned—challenge accepted? Chem Soc Rev 44:6094–6121
Frohlich E, Roblegg E (2016) Oral uptake of nanoparticles: human relevance and the role of in vitro systems. Arch Toxicol 90:2297–2314
Ge C, Tian J, Zhao Y, Chen C, Zhou R, Chai Z (2015) Towards understanding of nanoparticle-protein corona. Arch Toxicol 89:519–539
Gerloff K, Pereira DI, Faria N, Boots AW, Kolling J, Forster I, Albrecht C, Powell JJ, Schins RP (2013) Influence of simulated gastrointestinal conditions on particle-induced cytotoxicity and interleukin-8 regulation in differentiated and undifferentiated Caco-2 cells. Nanotoxicology 7:353–366
Gilbert B, Fakra SC, Xia T, Pokhrel S, Madler L, Nel AE (2012) The fate of ZnO nanoparticles administered to human bronchial epithelial cells. ACS Nano 6:4921–4930
Go MR, Bae SH, Kim HJ, Yu J, Choi SJ (2017) Interactions between food additive silica nanoparticles and food matrices. Front Microbiol 8:1013
Gong Y, Ji Y, Liu F, Li J, Cao Y (2017) Cytotoxicity, oxidative stress and inflammation induced by ZnO nanoparticles in endothelial cells: interaction with palmitate or lipopolysaccharide. J Appl Toxicol 37:895–901
Gu Y, Cheng S, Chen G, Shen Y, Li X, Jiang Q, Li J, Cao Y (2017) The effects of endoplasmic reticulum stress inducer thapsigargin on the toxicity of ZnO or TiO2 nanoparticles to human endothelial cells. Toxicol Mech Method 27:191–200
Institute of Medicine (2001) Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. The National Academies Press, Washington, DC
Jain A, Ranjan S, Dasgupta N, Ramalingam C (2016) Nanomaterials in food and agriculture: an overview on their safety concerns and regulatory issues. Crit Rev Food Sci Nutr 4–6. https://doi.org/10.1080/10408398.2016.1160363
Jiang Q, Li X, Cheng S, Gu Y, Chen G, Shen Y, Xie Y, Cao Y (2016) Combined effects of low levels of palmitate on toxicity of ZnO nanoparticles to THP-1 macrophages. Environ Toxicol Pharmacol 48:103–109
Kang T, Guan R, Chen X, Song Y, Jiang H, Zhao J (2013) In vitro toxicity of different-sized ZnO nanoparticles in Caco-2 cells. Nanoscale Res Lett 8:496–498
Kharazian B, Hadipour NL, Ejtehadi MR (2016) Understanding the nanoparticle-protein corona complexes using computational and experimental methods. Int J Biochem Cell Biol 75:162–174
Khare P, Sonane M, Nagar Y, Moin N, Ali S, Gupta KC, Satish A (2015) Size dependent toxicity of zinc oxide nano-particles in soil nematode Caenorhabditis elegans. Nanotoxicology 9:423–432
Lee JA, Kim MK, Song JH, Jo MR, Yu J, Kim KM, Kim YR, JM O, Choi SJ (2017) Biokinetics of food additive silica nanoparticles and their interactions with food components. Colloids Surf B Biointerfaces 150:384–392
Lefebvre DE, Venema K, Gombau L, Valerio LG Jr, Raju J, Bondy GS, Bouwmeester H, Singh RP, Clippinger AJ, Collnot EM, Mehta R, Stone V (2015) Utility of models of the gastrointestinal tract for assessment of the digestion and absorption of engineered nanomaterials released from food matrices. Nanotoxicology 9:523–542
Li Y, Zhang C, Liu L, Gong Y, Xie Y, Cao Y (2017) The effects of baicalein or baicalin on the colloidal stability of ZnO nanoparticles (NPs) and toxicity of NPs to Caco-2 cells. Toxicol Mech Methods 1–26
Lichtenstein D, Ebmeyer J, Knappe P, Juling S, Bohmert L, Selve S, Niemann B, Braeuning A, Thunemann AF, Lampen A (2015) Impact of food components during in vitro digestion of silver nanoparticles on cellular uptake and cytotoxicity in intestinal cells. Biol Chem 396:1255–1264
Liu F, Huang H, Gong Y, Li J, Zhang X, Cao Y (2017) Evaluation of in vitro toxicity of polymeric micelles to human endothelial cells under different conditions. Chem Biol Interact 263:46–54
Lopes S, Ribeiro F, Wojnarowicz J, Lojkowski W, Jurkschat K, Crossley A, Soares AM, Loureiro S (2014) Zinc oxide nanoparticles toxicity to Daphnia magna: size-dependent effects and dissolution. Environ Toxicol Chem 33:190–198
Mancini A, Imperlini E, Nigro E, Montagnese C, Daniele A, Orru S, Buono P (2015) Biological and nutritional properties of palm oil and palmitic acid: effects on health. Molecules 20:17339–17361
Martirosyan A, Bazes A, Schneider YJ (2014) In vitro toxicity assessment of silver nanoparticles in the presence of phenolic compounds—preventive agents against the harmful effect? Nanotoxicology 8:573–582
Martirosyan A, Grintzalis K, Polet M, Laloux L, Schneider YJ (2016) Tuning the inflammatory response to silver nanoparticles via quercetin in Caco-2 (co-)cultures as model of the human intestinal mucosa. Toxicol Lett 253:36–45
McClements, D. J., Xiao, H., and Demokritou, P (2017) Physicochemical and colloidal aspects of food matrix effects on gastrointestinal fate of ingested inorganic nanoparticles. Adv.Colloid Interface Sci 5–9. Ref Type: In Press
McCracken C, Dutta PK, Waldman WJ (2016) Critical assessment of toxicological effects of ingested nanoparticles. Environ Sci Nano 3:256–282
Moore TL, Rodriguez-Lorenzo L, Hirsch V, Balog S, Urban D, Jud C, Rothen-Rutishauser B, Lattuada M, Petri-Fink A (2015) Nanoparticle colloidal stability in cell culture media and impact on cellular interactions. Chem Soc Rev 44:6287–6305
Mu Q, David CA, Galceran J, Rey-Castro C, Krzeminski L, Wallace R, Bamiduro F, Milne SJ, Hondow NS, Brydson R, Vizcay-Barrena G, Routledge MN, Jeuken LJ, Brown AP (2014) Systematic investigation of the physicochemical factors that contribute to the toxicity of ZnO nanoparticles. Chem Res Toxicol 27:558–567
Sahu D, Kannan GM, Vijayaraghavan R (2014) Size-dependent effect of zinc oxide on toxicity and inflammatory potential of human monocytes. J Toxicol Environ Health A 77:177–191
Sambuy Y, De A,I, Ranaldi G, Scarino ML, Stammati A, Zucco F (2005) The Caco-2 cell line as a model of the intestinal barrier: influence of cell and culture-related factors on Caco-2 cell functional characteristics. Cell Biol Toxicol 21:1–26
Saptarshi SR, Duschl A, Lopata AL (2015) Biological reactivity of zinc oxide nanoparticles with mammalian test systems: an overview. Nanomedicine (London) 10:2075–2092
Shen C, James SA, de Jonge MD, Turney TW, Wright PF, Feltis BN (2013) Relating cytotoxicity, zinc ions, and reactive oxygen in ZnO nanoparticle-exposed human immune cells. Toxicol Sci 136:120–130
Shi LE, Li ZH, Zheng W, Zhao YF, Jin YF, Tang ZX (2014) Synthesis, antibacterial activity, antibacterial mechanism and food applications of ZnO nanoparticles: a review. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 31:173–186
Soenen SJ, Parak WJ, Rejman J, Manshian B (2015) (Intra)cellular stability of inorganic nanoparticles: effects on cytotoxicity, particle functionality, and biomedical applications. Chem Rev 115:2109–2135
Song Y, Guan R, Lyu F, Kang T, Wu Y, Chen X (2014) In vitro cytotoxicity of silver nanoparticles and zinc oxide nanoparticles to human epithelial colorectal adenocarcinoma (Caco-2) cells. Mutat Res 769:113–118
Song ZM, Chen N, Liu JH, Tang H, Deng X, Xi WS, Han K, Cao A, Liu Y, Wang H (2015) Biological effect of food additive titanium dioxide nanoparticles on intestine: an in vitro study. J Appl Toxicol 35:1169–1178
Taurozzi, J. S., Hackley, V. A., and Wiesner, M. R. (2012) Preparation of nanoparticle dispersions from powdered material using ultrasonic disruption. NIST Spec Publ 1200–2. 6–19 Ref Type: Electronic Citation
Vance ME, Kuiken T, Vejerano EP, McGinnis SP, Hochella MF Jr, Rejeski D, Hull MS (2015) Nanotechnology in the real world: Redeveloping the nanomaterial consumer products inventory. Beilstein J Nanotechnol 6:1769–1780
Wang H, LJ D, Song ZM, Chen XX (2013) Progress in the characterization and safety evaluation of engineered inorganic nanomaterials in food. Nanomedicine (London) 8:2007–2025
Wang Y, Yuan L, Yao C, Ding L, Li C, Fang J, Sui K, Liu Y, Wu M (2014) A combined toxicity study of zinc oxide nanoparticles and vitamin C in food additives. Nano 6:15333–15342
Xiong HM (2013) ZnO nanoparticles applied to bioimaging and drug delivery. Adv Mater 25:5329–5335
Yang X, Shao H, Liu W, Gu W, Shu X, Mo Y, Chen X, Zhang Q, Jiang M (2015) Endoplasmic reticulum stress and oxidative stress are involved in ZnO nanoparticle-induced hepatotoxicity. Toxicol Lett 234:40–49
Yin H, Casey PS, McCall MJ, Fenech M (2015) Size-dependent cytotoxicity and genotoxicity of ZnO particles to human lymphoblastoid (WIL2-NS) cells. Environ Mol Mutagen 56:767–776
Zhou Y, Fang X, Gong Y, Xiao A, Xie Y, Liu L, Cao Y (2017) The interactions between ZnO nanoparticles (NPs) and alpha-linolenic acid (LNA) complexed to BSA did not influence the toxicity of ZnO NPs on HepG2 cells. Nanomaterials (Basel) 7:E91
Acknowledgements
We appreciate Prof. Peter Moller (University of Copenhagen) to kindly provide the ZnO NPs (NM110) to us.
Funding
This study was funded by the Scientific Research Fund of Hunan Provincial Education Department (15C1331), Xiangtan University start-up grant (15QDZ14), and Xiangtan University grant (15XZX18).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Electronic supplementary material
ESM 1
(PDF 503 kb)
Rights and permissions
About this article
Cite this article
Gong, Y., Liu, L., Li, J. et al. The presence of palmitate affected the colloidal stability of ZnO NPs but not the toxicity to Caco-2 cells. J Nanopart Res 19, 335 (2017). https://doi.org/10.1007/s11051-017-4038-9
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11051-017-4038-9