Integrative Metabolomics, Proteomics and Transcriptomics Analysis Reveals Liver Toxicity of Mesoporous Silica Nanoparticles

Abstract

As pharmaceutical excipients, mesoporous silica nanoparticles (MSNs) have attracted considerable concern based on potential risks to the public. The impact of MSNs on biochemical metabolism is poorly understood, and few studies have compared the effects of MSNs administered via different routes. To evaluate the hepatotoxicity of MSNs, metabolomics, proteomics and transcriptomic analyses were performed in mice after intravenous (20 mg/kg/d) or oral ad-ministration (200 mg/kg/d) of MSNs for 10 days. Intravenous injection induced significant hepatic injury based on pathological inspection and increased the levels of AST/ALT and the inflammatory factors IL-6, IL-1β and TNF-a. Omics data suggested intravenous administration of MSNs perturbed the following metabolites: succinate, hypoxanthine, GSSG, NADP+, NADPH and 6-phosphogluconic acid. In addition, increases in GPX, SOD3, G6PD, HK, and PFK at proteomic and transcriptomic levels suggested elevation of glycolysis and pentose phosphate pathway, synthesis of glutathione and nucleotides, and antioxidative pathway activity, whereas oxidative phosphorylation, TCA and mitochondrial energy metabolism were reduced. On the other hand, oral administration of MSNs disturbed inflammatory factors and metabolites of ribose-5-phosphate, 6-phosphogluconate, GSSG, and NADP+ associated with the pentose phosphate pathway, glutathione synthesis and oxidative stress albeit to a lesser extent than intravenous injection despite the administration of a ten-fold greater dose. Overall, systematic biological data suggested that intravenous injection of nanoparticles of pharmaceutical excipients substantially affected hepatic metabolism function and induced oxidative stress and inflammation, whereas oral administration exhibited milder effects compared with intravenous injection.

Mesoporous Silica Nanoparticles as a Potential Nanoplatform: Therapeutic Applications and Considerations

“…A.M. Mahmoud et al’s [ 153 ] study showed that MSNs significantly induced dose-dependent damage in liver and kidney in rats via MSNs-triggered oxidative stress, inflammatory signals, and fibrosis. Furthermore, in in vivo studies by J. Li et al [ 154 ], MSNs were found to affect hepatic metabolism after intravenous (IV) administration at a concentration of 20 mg/kg/day or after oral administration at 200 mg/kg/day for 10 days. Further pathological examination after IV administration of MSNs revealed induction of hepatic injury with increasing levels of AST/ALT and inflammatory factors, such as IL-1β, IL-6, and TNF-α.…”

Shape and Shear Stress Impact on the Toxicity of Mesoporous Silica Nanoparticles: In Vitro and In Vivo Evidence

“…Currently, some studies have focused on the in vivo safety evaluation of MSNs after different administration routes, including oral administration, ,, intravenous injection, − intraperitoneal injection, subcutaneous injection, intramuscular injection, and ophthalmic administration . However, the effect of shape and mechanisms on MSN biotoxicity is still insufficient, especially under physiological dynamic conditions in vivo after intravenous injection.…”

Nano‐omics: Frontier fields of fusion of nanotechnology

“…At proteomic and transcriptomic levels, GPX, SOD3, G6PD, HK, and PFK increase showed that elevation of glycolysis and pentose phosphate pathway, synthesis of glutathione and nucleotides, and antioxidative pathway activity, whereas oxidative phosphorylation, TCA and mitochondrial energy metabolism were reduced. These results suggested that oral administration exhibited milder effects than intravenous injection 43 . Nanomaterials will also have an impact on the original diseases of the human body.…”

“…These results suggested that oral administration exhibited milder effects than intravenous injection. 43 Nanomaterials will also have an impact on the original diseases of the human body. The presence of SiNPs had a significant impact on the hepatic metabolic profile of ApoE mice, particularly affecting amino acid and lipid metabolism.…”