Integrated transcriptomics and metabolomics analysis reveals the biomolecular mechanisms associated to the antitumoral potential of a novel silver-based core@shell nanosystem

Abstract

A combination of omics techniques (transcriptomics and metabolomics) has been used to elucidate the mechanisms responsible for the antitumor action of a nanosystem based on a Ag core coated with mesoporous silica on which transferrin has been anchored as a targeting ligand against tumor cells (Ag@MSNs-Tf). Transcriptomics analysis has been carried out by gene microarrays and RT-qPCR, while high-resolution mass spectrometry has been used for metabolomics. This multi-omics strategy has enabled the discovery of the effect of this nanosystem on different key molecular pathways including the glycolysis, the pentose phosphate pathway, the oxidative phosphorylation and the synthesis of fatty acids, among others.

Keywords: ATP synthesis; Cancer treatment; Electron transport chain complex; Mesoporous silica nanoparticles; Metabolomics; Transcriptomics.

Fig. 1

Concentration levels of ATP, ADP, NADH, and NAD⁺ metabolites in HepG2 cells after exposure to 10 µg/mL of Ag@MSNs-Tf for 72 h. Data were analyzed by ANOVA followed by Bonferroni’s multiple-comparison test. Statistical significance: *p < 0.05; ****p < 0.0001

Fig. 2

mRNA levels of genes involved in the electron transport chain complexes in HepG2 cells exposed to 10 µg/mL of Ag@MSNs-Tf for 72 h. Data were analyzed by ANOVA followed by Bonferroni’s multiple-comparison test. Statistical significance: *p < 0.05; ****p < 0.0001

Fig. 3

PCA results from the GC–MS data. A 2D scores plot of the first principal component (PC1) versus the second principal component (PC2) for control (n = 7) (red area) and cells treated with 10 µg/mL of Ag@MSNs-Tf for 72 h (n = 7) (green area). B Loading plot of PC1 versus PC2 for the 26 quantified metabolites (the number of each metabolite correlates with the identified metabolites as shown in Supplemental Table S3)

Fig. 4

Illustration of the main biochemical pathways responsible for the antitumoral potential of Ag@MSNs-Tf