Abstract

Zinc oxide (ZnO) nanoparticles (NPs) have been widely used for food fortification, because zinc is essential for many enzyme and hormone activities and cellular functions, but public concern about their potential toxicity is increasing. Interactions between ZnO and biomatrices might affect the oral absorption, distribution, and toxicity of ZnO, which may be influenced by particle size. In this study, ZnO interactions with biomatrices were investigated by examining the physicochemical properties, solubility, protein fluorescence quenching, particle–protein corona, and intestinal transport with respect to the particle size (bulk vs. nano) in simulated gastrointestinal (GI) and plasma fluids and in rat-extracted fluids. The results demonstrate that the hydrodynamic radii and zeta potentials of bulk ZnO and nano ZnO in biofluids changed in different ways, and that nano ZnO induced higher protein fluorescence quenching than bulk ZnO. However, ZnO solubility and its intestinal transport mechanism were unaffected by particle size. Proteomic analysis revealed that albumin, fibrinogen, and fibronectin play roles in particle–plasma protein corona, regardless of particle size. Furthermore, nano ZnO was found to interact more strongly with plasma proteins. These observations show that bulk ZnO and nano ZnO interact with biomatrices in different ways and highlight the need for further study of their long-term toxicity.

Highlights

  • Zinc oxide (ZnO) is widely utilized in industry because of its ultraviolet (UV) protective, nutritional, and anti-microbial properties [1,2,3]

  • ZnO NPs have been used as food fortifications and agricultural fertilizers, because zinc plays an important role in the metabolism and protein synthesis, and in the regulation of gene expression and enzyme and hormone activities [6,7,8]

  • The complementary system is an essential part of the immune system [41,42], which was only found in nano ZnO–plasma protein corona. These findings show that ZnO–plasma protein interactions are dependent on particle size and suggest that nano ZnO is more likely to affect immune response than bulk ZnO

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Summary

Introduction

Zinc oxide (ZnO) is widely utilized in industry because of its ultraviolet (UV) protective, nutritional, and anti-microbial properties [1,2,3]. ZnO NPs have been used as food fortifications and agricultural fertilizers, because zinc plays an important role in the metabolism and protein synthesis, and in the regulation of gene expression and enzyme and hormone activities [6,7,8]. Many studies have been performed on the toxicity of ZnO NPs in cell lines and animal models [9,10,11,12], and some conflicting results have been reported. Particles administered orally encounter diverse biological matrices, such as gastrointestinal (GI) fluids and blood, and these interactions lead to the formation of particle–biomatrix corona, which can alter their physicochemical property, biological interaction, and biological fate [13,14]. The rmepaojortreidtythoaftstthuedNiePss–opnlatshmisatporpoitceihnaivneterfoacctuiosnedcaonnbtehiemdpelitceartmedininatiimonmuonf oNloPgsicianltreercaocgtnioitniosnw, ith plasmaolpecruoltaerintsa,rgthetoiungg,hbtihoedsisetriinbtuetriaocnt,ioannsdairnetrsaucreellluylaarffuecptteadkeb[y18p]a. rTtihcelemsiazjoer.itIyndoefesdtu, dZinesOoNnPthsiws ere repotrotepdictohaevxehifboictuasehdigohnertchyetodteotxeircmitiynantidoninoflfaNmPmsaitniotenrarectsipoonnsswe itthhanplmasimcrao ZprnoOteinsh, uthmoaunghmothneosceytes, and itnhteeirrascitzioe-ndseaprensduerneltycayftfoetcotexdicibty ptoawrtaicrlde hsiuzme. aInndleuendg, ZepniOthNelPiasl wceelrlse wreapsoartlesdo dtoemexohnibsittraatehdig[h1e9r–21]

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