TY - JOUR
T1 - Assessing nanotoxicity of food-relevant particles
T2 - A comparative analysis of cellular responses in cell monolayers versus 3D gut epithelial cultures
AU - Gautam, Archana
AU - Lim, Hui Kheng
AU - Li, Jasmine Jia En
AU - Hughes, Christopher Owen
AU - Yeo, Calvin Wee Sing
AU - Rakshit, Moumita
AU - Leavesley, David Ian
AU - Lim, Michelle Jing Sin
AU - Tan, Joseph Choon Wee
AU - Tan, Li Yi
AU - Chan, Joanne Sheot Harn
AU - Smith, Benjamin Paul Chapman
AU - Ng, Kee Woei
N1 - Publisher Copyright:
© 2024 Elsevier Ltd
PY - 2024/11
Y1 - 2024/11
N2 - Engineered nanoparticles (NPs) are extensively used in the food industry, yet safety concerns remain. The lack of validated methodologies is a bottleneck towards resolving this uncertainty. Hence, the current study aims to compare two cell models by examining the toxicological impacts of two food-relevant NPs (SiO2 and Ag) on intestinal epithelia using monolayer Caco-2 cells and full-thickness 3D tissue models of human small intestines (EpiIntestinal™). Comprehensive characterization and dosimetric analysis of the NPs were performed to determine effective doses and model realistic exposures. Neither genotoxicity nor cytotoxicity were detected in the 3D tissues after NP treatment, while the 2D cultures exhibited cytotoxic response from Ag NP treatment for 24 h at 1 μg/ml. Hyperspectral imaging and transmission electron microscopy confirmed uptake of both NPs by cells in both 2D and 3D culture models. Ag NPs caused an increase in autophagy, whereas SiO2 NPs induced increased cytoplasmic vacuolization. Based on realistic exposure levels studied, the 3D small intestinal tissue model was found to be more resilient to NP treatment compared to 2D cell monolayers. This comparative approach towards toxicological assessment of food relevant NPs could be used as a framework for future analysis of NP behavior and nanotoxicity in the gut.
AB - Engineered nanoparticles (NPs) are extensively used in the food industry, yet safety concerns remain. The lack of validated methodologies is a bottleneck towards resolving this uncertainty. Hence, the current study aims to compare two cell models by examining the toxicological impacts of two food-relevant NPs (SiO2 and Ag) on intestinal epithelia using monolayer Caco-2 cells and full-thickness 3D tissue models of human small intestines (EpiIntestinal™). Comprehensive characterization and dosimetric analysis of the NPs were performed to determine effective doses and model realistic exposures. Neither genotoxicity nor cytotoxicity were detected in the 3D tissues after NP treatment, while the 2D cultures exhibited cytotoxic response from Ag NP treatment for 24 h at 1 μg/ml. Hyperspectral imaging and transmission electron microscopy confirmed uptake of both NPs by cells in both 2D and 3D culture models. Ag NPs caused an increase in autophagy, whereas SiO2 NPs induced increased cytoplasmic vacuolization. Based on realistic exposure levels studied, the 3D small intestinal tissue model was found to be more resilient to NP treatment compared to 2D cell monolayers. This comparative approach towards toxicological assessment of food relevant NPs could be used as a framework for future analysis of NP behavior and nanotoxicity in the gut.
KW - 3D models
KW - Genotoxicity
KW - Intestine
KW - Nanoparticles
KW - Nanotoxicology
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U2 - 10.1016/j.fct.2024.115055
DO - 10.1016/j.fct.2024.115055
M3 - Article
C2 - 39396697
AN - SCOPUS:85206251499
SN - 0278-6915
VL - 193
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
M1 - 115055
ER -