Short-Term Oral Administration of Mesoporous Silica Nanoparticles Potentially Induced Colon Inflammation in Rats Through Alteration of Gut Microbiota

Abstract

Mesoporous silica (MSNs) have attracted considerable attention for its application in the field of drug delivery and biomedicine due to its high surface area, large pore volume, and low toxicity. Recently, numerous studies revealed that gut microbiota is of critical relevance to host health. However, the toxicological studies of MSNs were mainly based on the degradation, biodistribution, and excretion in mammalian after oral administration for now. Here in this study, we explored the impacts of oral administration of three kinds of MSNs on gut microbiota in rats to assess its potential toxicity. Methods: Forty rats were divided into four groups: control group; Mobil Composition of Matter No. 41 type mesoporous silica (MCM-41) group; Santa Barbara Amorphous-15 type mesoporous silica (SBA-15) group, and biodegradable dendritic center-radial mesoporous silica nanoparticle (DMSN) group. Fecal samples were collected 3 days and 7 days after the intake of MSNs and analyzed with high throughput sequencing. Gastric tissues in rats were obtained after dissection for the histological study. Results: Three different MSNs (MCM-41, SBA-15, and DMSN) were successfully prepared in this study. The pore size of three MSNs was calculated similarly as (3.54 ± 0.15) nm, (3.48 ± 0.21) nm, and (3.45 ± 0.17) nm according to the BET & BJH model, respectively, while the particle size of MCM-41, SBA-15 and DMSN was around 209.2 nm, 1349.56 nm, and 244.4 nm, respectively. In the gene analysis of 16S rRNA, no significant changes in the diversity and richness were found between groups, while Verrucomicrobia decreased and Candidatus Saccharibacteria increased in MCM-41 treated groups. Meanwhile, no inflammatory and erosion symptoms were observed in the morphological analysis of the colons, except the MCM-41 treated group. Conclusion: Three different MSNs, MCM-41, SBA-15, and DMSN were successfully prepared, and this study firstly suggested the impact of MSNs on the gut microbiota, and further revealing the potential pro-inflammatory effects of oral administration of MCM-41 was possibly through the changing of gut microbiota.

Amorphous silica nanoparticles and the human gut microbiota: a relationship with multiple implications

“…In contrast, enhancement of microbial species richness and diversity has been described in mice exposed to ASNP through oral administration, with an increase of genera Alistipes , Lactobacillus , Oscillibacter and Prevotella , and a decrease of Bacteroides [ 87 ]. More recently, several studies [ 54 , 88 – 90 ] have presented clear-cut evidence of microbiota changes associated with the toxic effects (e.g. altered transport and barrier functions, inflammatory changes, decrease in mucus, increase of LPS absorption, hepatotoxicity) observed after ASNP exposure.…”

Advances in nanomaterial-based targeted drug delivery systems

“…The use of nanoparticles for insulin transport or gene delivery has also shown excellent therapeutic effects in diabetic model mice ( Lamson et al, 2020 ; Sudhakar et al, 2020 ). Besides improving diabetes treatment options, oral nanoparticles have shown great therapeutic promise in other diseases, such as intestinal disorders, bacterial infectious diseases, and oncology ( Kim et al, 2019 ; Shen et al, 2019 ; Ndayishimiye et al, 2021 ; Wang J. et al, 2021 ; Yu et al, 2021 ; Li et al, 2022 ; Zhang G. et al, 2022 ). Additionally, a pioneering attempt to synthesize orally administered nanoparticles has recently been conducted by researchers to easily prepare and use gold nanoparticles (GNP) ( Ndayishimiye et al, 2021 ) in the synthesis conditions.…”

Interactions between Nanoparticles and Intestine

“…However, some researchers focused on the effects of the "pure" NPs, showing alterations in the microbiota composition. Chandrarathna et al observed an increase in Bacteroidetes abundance and a reduction in Firmicutes after the oral administration of pectin NPs [26], whereas Yu et al detected variations in microbiota composition after a 7-day treatment with mesoporous silica NPs [27]. Variations in microbiota, but also in plasma metabolome were detected by Landsiedel et al, who treated rats by oral gavage of silicon dioxide (SiO 2 ) or Ag NPs for 28 days, thus mimicking a "chronic" exposure [28].…”