Abstract:Amorphous silica nanoparticles (NPs) possess unique material properties that make them ideal for many different applications. However, the impact of these materials on human and environmental health needs to be established. We investigated nonporous silica NPs both bare and modified with amine functional groups (3-aminopropyltriethoxysilane (APTES)) in order to evaluate the effect of surface chemistry on biocompatibility. In vitro data showed there to be little to no cytotoxicity in a human lung cancer epithel… Show more
“…It was reported that SiO 2 NPs modified with amine functional groups induced less serious lung inflammation and possessed better biocompatibility. 38 Lu et al found that amino and carboxyl surface modification mitigated the hepatic toxicity of SiO 2 NPs. 39 However, there is a lack of more meticulous and systemic studies about the effects of surface modification on the toxicity of SiO 2 NPs.…”
The liver is one of the target organs of silica nanoparticles (SiO
2
NPs) but the toxic mechanism on the liver still remains unclear. This study aimed to explore the hepatic toxicity and its mechanism through repeated intravenous exposure to SiO
2
NPs in ICR mice. Results indicated that SiO
2
NPs could be distributed in hepatocytes, Kupffer cells, and hepatic stellate cells, and induce hepatic dysfunction as well as granuloma formation in the liver. The increase of lipid peroxide level and decrease of antioxidant enzyme activities in the liver indicated that SiO
2
NPs could induce hepatic oxidative damage. SiO
2
NPs induced hepatocytes’ apoptosis shown by morphological examination and TUNEL assay. The results of Masson’s trichrome staining and hydroxyproline assay showed hyperplasia of collagen fibers in the liver, suggesting SiO
2
NPs caused liver fibrosis, and it was promoted by oxidative damage and hepatocytes’ apoptosis. The results of Western blot analysis and immunohistochemical staining indicated that the activation of TGF-β
1
/Smad3 signaling pathway played an important role in this pathophysiological process. The results suggested that oxidative damage and hepatocyte apoptosis activated TGF-β
1
/Smad3 signaling pathway, and thus promoted the process of liver fibrosis induced by intravenous injection of SiO
2
NPs in mice. This study, for the first time, investigated liver fibrosis and its related mechanism induced by repeated intravenous exposure of amorphous SiO
2
NPs, and provides important experimental evidence for safety evaluation of SiO
2
NPs, especially in biomedical application.
“…It was reported that SiO 2 NPs modified with amine functional groups induced less serious lung inflammation and possessed better biocompatibility. 38 Lu et al found that amino and carboxyl surface modification mitigated the hepatic toxicity of SiO 2 NPs. 39 However, there is a lack of more meticulous and systemic studies about the effects of surface modification on the toxicity of SiO 2 NPs.…”
The liver is one of the target organs of silica nanoparticles (SiO
2
NPs) but the toxic mechanism on the liver still remains unclear. This study aimed to explore the hepatic toxicity and its mechanism through repeated intravenous exposure to SiO
2
NPs in ICR mice. Results indicated that SiO
2
NPs could be distributed in hepatocytes, Kupffer cells, and hepatic stellate cells, and induce hepatic dysfunction as well as granuloma formation in the liver. The increase of lipid peroxide level and decrease of antioxidant enzyme activities in the liver indicated that SiO
2
NPs could induce hepatic oxidative damage. SiO
2
NPs induced hepatocytes’ apoptosis shown by morphological examination and TUNEL assay. The results of Masson’s trichrome staining and hydroxyproline assay showed hyperplasia of collagen fibers in the liver, suggesting SiO
2
NPs caused liver fibrosis, and it was promoted by oxidative damage and hepatocytes’ apoptosis. The results of Western blot analysis and immunohistochemical staining indicated that the activation of TGF-β
1
/Smad3 signaling pathway played an important role in this pathophysiological process. The results suggested that oxidative damage and hepatocyte apoptosis activated TGF-β
1
/Smad3 signaling pathway, and thus promoted the process of liver fibrosis induced by intravenous injection of SiO
2
NPs in mice. This study, for the first time, investigated liver fibrosis and its related mechanism induced by repeated intravenous exposure of amorphous SiO
2
NPs, and provides important experimental evidence for safety evaluation of SiO
2
NPs, especially in biomedical application.
“…The polydispersity index (PDI) and particle-size diameters of the amine-modified SiO 2 NPs are determined and listed in Figure 6a-d. All amine-modified SiO 2 NPs formed aggregates or cluster at pH 7 and their sizes were altered by changing the pH of aqueous solutions either in acidic or alkaline aqueous solutions (Figure 6a-d). The amine-modified silica nanomaterials tend to form interparticle network and consequently gelation, which increased with increasing the amine contents [35][36][37][38][39]. The increasing of the particle sizes of SiO 2 -10-10 NPs (Figure 5d) more than other amine-modified SiO 2 NPs agrees with the previous works [35][36][37][38][39] and elucidates the increasing of amine contents on its surfaces as confirmed from FTIR and TGA analysis ( Figures 1a-d and 2a-d, respectively).…”
Section: Effect Of Ph On the Surface And Particle Sizes Of Sio 2 Npsmentioning
In this work, new smart mesoporous amine-functionalized silica nanoparticles were prepared from hydrolyzing microgels based on N-isopropyl acrylamide-co-vinyltrimethoxysilane microgels with tetraethoxysilicate and 3-aminopropyltriethoxysilane by sol-gel method. The thermal stability and Fourier transform infrared were used to determine the amine contents of the silica nanoparticles. The pH sensitivity of the synthesized silica nanoparticles in their aqueous solutions was evaluated by using dynamic light scattering (DLS) and zeta potential measurements. The porosity of the amine-functionalized silica nanoparticles was evaluated from a transmittance electron microscope and Brunauer-Emmett-Teller (BET) plot. The results have positively recommended the pH-sensitive amine-functionalized silica nanoparticles as one of the effective nano-adsorbent to remove 313 mg·g−1 of CB-R250 water pollutant.
“…One possible reason for the discrepancy in the findings regarding the role of amine‐modifications of the silica surface for toxicity might stem from differences in the quantitative coverage by the functional groups. It is assumed that replacement of reactive silanol groups by amino groups prevents their detrimental interaction with cells . However, it has not been determined yet, how much of the silica surface needs to be covered by amino groups to suppress toxicity.…”
Here, amorphous silica nanoparticles (NPs), one of the most abundant nanomaterials, are used as an example to illustrate the utmost importance of surface coverage by functional groups which critically determines biocompatibility. Silica NPs are functionalized with increasing amounts of amino groups, and the number of surface exposed groups is quantified and characterized by detailed NMR and fluorescamine binding studies. Subsequent biocompatibility studies in the absence of serum demonstrate that, irrespective of surface modification, both plain and amine‐modified silica NPs trigger cell death in RAW 264.7 macrophages. The in vitro results can be confirmed in vivo and are predictive for the inflammatory potential in murine lungs. In the presence of serum proteins, on the other hand, a replacement of only 10% of surface‐active silanol groups by amines is sufficient to suppress cytotoxicity, emphasizing the relevance of exposure conditions. Mechanistic investigations identify a key role of lysosomal injury for cytotoxicity only in the presence, but not in the absence, of serum proteins. In conclusion, this work shows the critical need to rigorously characterize the surface coverage of NPs by their constituent functional groups, as well as the impact of serum, to reliably establish quantitative nanostructure activity relationships and develop safe nanomaterials.
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