Diverse transcriptomic response of cellular system following low-dose exposure of mesoporous nanoparticles

Abstract

Mesoporous nanoparticles are an interesting drug delivery system that has generated considerable attention in the biomedical sector. Despite recent attempts to conduct safety assessments using traditional methods based on phenotypic data, our understanding of the underlying molecular processes produced by mesoporous NPs is still in its infancy. In the present study, RNA sequencing was used to assess the biological perturbations and the pathways induced in response to early exposure of two different mesoporous NPs; mesoporous silica NPs and mesoporous carbon NPs in human liver hepatocellular carcinoma cells. In order to better understand the risks associated with NPs, it is required to consider the initial low dose exposure effects that mimic the real exposure scenario. No overt toxicity was detected in the MTT assay when performed at 6 hours at low concentrations (MCN 25 g/ml and MSN 15 g/ml) of NPs; thus, RNA sequencing was used at this concentration. Our transcriptomics analysis showed significant differences in the expression of many genes after exposure to both NPs. Surprisingly, both NPs frequently deregulated 52.9 percent of upregulated and 42 percent of downregulated genes. Gene ontology categories, in particular, revealed comparable perturbations of biological reactions in the cellular system. HepG2 cells reacted to mesoporous NPs by allowing alterations in genes involved in cytoskeleton reorganisation (ATAT1, DMTN, PTK2 and PFN2). Exposure to mesoporous NPs increased transcripts expressing ubiquitin ligase (RNF187, ARIH2, VHL, and RAB40C), transferase (FBXO3 and WDSUB1), conjugating (UBE2J2), and also proteasomal subunits (PSMD2, PSMD13) enzymes, indicating that protein turnover rates are altered in response to environmental damage. In addition, DNA damage and DNA damage checkpoint genes were upregulated, indicating that NPs induced stress in the cells. These finding showed low dosage acute exposure have comparable responses between mesoporous NPs.

Proteomics analysis of MSN, MWCNT and ZnO nanoparticle-induced alteration in prepubertal rat ovary

“…Recently, Mittal D. revealed that exposure to MSN, ZnO and mesoporous carbon nanoparticles (MCN) resulted in the upregulation of over 200 ubiquitination pathway genes and the downregulation of over 100 transcripts. 48,49…”

“…Recently, Mittal D. revealed that exposure to MSN, ZnO and mesoporous carbon nanoparticles (MCN) resulted in the upregulation of over 200 ubiquitination pathway genes and the downregulation of over 100 transcripts. 48,49 We obtained information to classify the interaction based on the topological classification. We created the collective mapping of proteins using PPI interaction.…”

ZnO nanoparticles and SWCNT induced general stress response pathway in HepG2 cells at non-cytotoxic doses revealed by RNA sequencing

“…Additionally our another study was based on the transcriptomic analysis for the effect of MCN (Mesoporous carbon nanoparticles) and MSN in liver hepatoma cells that describes the regulation of common molecular pathways during initial interaction with the cellular system. These NPs perturbed pathways including DNA damage, repair, cell cycle regulation, transcription and ubiquitination are common among both MCN and MSN (Mittal et al, 2022).…”