scholarly journals Mesoporous Silica Nanoparticles Trigger Liver and Kidney Injury and Fibrosis Via Altering TLR4/NF-κB, JAK2/STAT3 and Nrf2/HO-1 Signaling in Rats

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 528 ◽  
Author(s):  
Ayman M. Mahmoud ◽  
Ekram M. Desouky ◽  
Walaa G. Hozayen ◽  
May Bin-Jumah ◽  
El-Shaymaa El-Nahass ◽  
...  
Keyword(s):  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Signaling Pathways ◽  
Mesoporous Silica Nanoparticles ◽  
Kidney Injury ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Liver And Kidney

Mesoporous silica nanoparticles (MSNs) represent a promising inorganic platform for multiple biomedical applications. Previous studies have reported MSNs-induced hepatic and renal toxicity; however, the toxic mechanism remains unclear. This study aimed to investigate MSNs-induced hepatic and nephrotoxicity and test the hypothesis that altered TLR4/MyD88/NF-κB, JAK2/STAT3, and Nrf2/ARE/HO-1 signaling pathways mediate oxidative stress, inflammation, and fibrosis induced by MSNs. Rats were administered 25, 50, 100, and 200 mg/kg MSNs for 30 days, and samples were collected for analyses. MSNs induced functional and histologic alterations, increased the levels of reactive oxygen species (ROS), lipid peroxidation and nitric oxide, suppressed antioxidants, and Nrf2/HO-1 signaling in the liver and kidney of rats. MSNs up-regulated the expression of liver and kidney TLR4, MyD88, NF-κB p65, and caspase-3 and increased serum pro-inflammatory cytokines. In addition, MSNs activated the JAK2/STAT3 signaling pathway, down-regulated peroxisome proliferator activated receptor gamma (PPARγ), and promoted fibrosis evidenced by the increased collagen expression and deposition. In conclusion, this study conferred novel information on the role of ROS and deregulated TLR4/MyD88/NF-κB, JAK2/STAT3, PPARγ, and Nrf2/ARE/HO-1 signaling pathways in MSNs hepatic and nephrotoxicity. These findings provide experimental evidence for further studies employing genetic and pharmacological strategies to evaluate the safety of MSNs for their use in nanomedicine.

Atorvastatin (ATV)-Loaded Lipid Bilayer-Coated Mesoporous Silica Nanoparticles Enhance the Therapeutic Efficacy of Acute Kidney Injury

2021 ◽  
Vol 17 (9) ◽  
pp. 1754-1764
Author(s):  
Guanjie Zhao ◽  
Na Li ◽  
Min Yin ◽  
Mingzhu Xu
Keyword(s):  
Acute Kidney Injury ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Lipid Bilayer ◽  
Therapeutic Efficacy ◽  
Mesoporous Silica Nanoparticles ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Tubular Structure ◽  
Remarkable Improvement

Background: Acute kidney injury (AKI) increases the risk of chronic kidney disease. Atorvastatin (ATV)-loaded lipid bilayer-coated mesoporous silica nanoparticles (L-AMSNs) were synthesized, and their physicochemical parameters were characterized. L-AMSNs exhibited excellent stability; it did not increase in size over time, indicating that the lipid membrane coating prohibited mesoporous silica nanoparticles (MSNs) coalescence. Results: The rate of drug release differed significantly between AMSNs and L-AMSNs at all tested time points. A remarkable improvement in hydrogen peroxide (H2O2)-treated human umbilical vein endothelial cell (HUVEC) viability was observed after treatment with L-AMSNs; the malondialdehyde (MDA) level was significantly reduced compared to control cells. The extent of apoptosis was only 15% that of control H2O2-treated cells. L-AMSNs induced a remarkable decrease in the levels of pro-inflammatory cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-6), showing the therapeutic potential of nanocarrier-based ATV. L-AMSNs significantly increased the superoxide dismutase level and decreased the MDA level, indicating superior anti-inflammatory activity under conditions of oxidative stress. The L-AMSN showed a remarkable improvement in the outer stripe of outer medulla (OSOM) region and maintained the tubular structure of the kidney tissue. Besides, kidney injury score of L-AMSN is significantly lower compared to that of LPS-AKI and ATV indicating the excellent therapeutic efficacy of nanoparticulate system based L-AMSN. Conclusions: Nanoparticles system-based L-AMSNs maintained the tubular structure of kidney tissue, indicating excellent therapeutic efficacy. After clinical translation, L-AMSNs could serve as a promising treatment for AKI.

scholarly journals Mesoporous Silica Nanoparticles Facilitate Delivery of siRNA to Shutdown Signaling Pathways in Mammalian Cells

Small ◽  
2010 ◽  
Vol 6 (11) ◽  
pp. 1185-1190 ◽  
Author(s):  
Christopher Hom ◽  
Jie Lu ◽  
Monty Liong ◽  
Hanzhi Luo ◽  
Zongxi Li ◽  
...  
Keyword(s):  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Signaling Pathways ◽  
Mammalian Cells ◽  
Mesoporous Silica Nanoparticles

Recent Advances in Application of Azobenzenes Grafted on Mesoporous Silica Nanoparticles in Controlled Drug Delivery Systems Using Light as External Stimulus

2020 ◽  
Vol 20 (11) ◽  
pp. 1001-1016
Author(s):  
Sandra Ramírez-Rave ◽  
María Josefa Bernad-Bernad ◽  
Jesús Gracia-Mora ◽  
Anatoly K. Yatsimirsky
Keyword(s):  
Drug Delivery ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Drug Delivery Systems ◽  
Mesoporous Silica Nanoparticles ◽  
High Surface ◽  
Delivery Systems ◽  
Surface Reactivity ◽  
External Stimulus ◽  
Recent Advances

Hybrid materials based on Mesoporous Silica Nanoparticles (MSN) have attracted plentiful attention due to the versatility of their chemistry, and the field of Drug Delivery Systems (DDS) is not an exception. MSN present desirable biocompatibility, high surface area values, and a well-studied surface reactivity for tailoring a vast diversity of chemical moieties. Particularly important for DDS applications is the use of external stimuli for drug release. In this context, light is an exceptional alternative due to its high degree of spatiotemporal precision and non-invasive character, and a large number of promising DDS based on photoswitchable properties of azobenzenes have been recently reported. This review covers the recent advances in design of DDS using light as an external stimulus mostly based on literature published within last years with an emphasis on usually overlooked underlying chemistry, photophysical properties, and supramolecular complexation of azobenzenes.

Fluorescent spherical mesoporous silica nanoparticles loaded with emodin: Synthesis, cellular uptake and anticancer activity

2021 ◽  
Vol 119 ◽  
pp. 111619
Author(s):  
Paul Jänicke ◽  
Claudia Lennicke ◽  
Annette Meister ◽  
Barbara Seliger ◽  
Ludger A. Wessjohann ◽  
...  
Keyword(s):  
Mesoporous Silica ◽  
Anticancer Activity ◽  
Silica Nanoparticles ◽  
Cellular Uptake ◽  
Mesoporous Silica Nanoparticles
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