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

Abstract

AbstractMesoporous nanoparticles (NPs) 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 (MSN) and mesoporous carbon NPs (MCN) 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, we have selected this dose for RNA sequencing analysis. 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. These results may add further knowledge in conceptualization of Safer-by-Design strategy of NPs in biomedical field.