Abstract

The unique physicochemical properties make inorganic nanoparticles (INPs) an exciting tool in diagnosis and disease management. However, as INPs are relatively difficult to fully degrade and excrete, their unintended accumulation in the tissue might result in adverse health effects. Herein, we provide a methylome–transcriptome framework for chronic effects of INPs, commonly used in biomedical applications, in human kidney TH-1 cells. Renal clearance is one of the most important routes of nanoparticle excretion; therefore, a detailed evaluation of nanoparticle-mediated nephrotoxicity is an important task. Integrated analysis of methylome and transcriptome changes induced by INPs (PEG-AuNPs, Fe3O4NPs, SiO2NPs, and TiO2NPs) revealed significantly deregulated genes with functional classification in immune response, DNA damage, and cancer-related pathways. Although most deregulated genes were unique to individual INPs, a relatively high proportion of them encoded the transcription factors. Interestingly, FOS hypermethylation inversely correlating with gene expression was associated with all INPs exposures. Our study emphasizes the need for a more comprehensive investigation of INPs’ biological safety, especially after chronic exposure.Graphical abstract

Highlights

  • Inorganic nanoparticles (INPs) have been widely used for a plethora of biomedical applications due to their unique physicochemical properties

  • We have shown that none of the studied INPs (i.e., AuNPs coated with polyethylene glycol – PEGAuNPs, ­Fe3O4NPs, ­SiO2NPs, and ­TiO2NPs), currently used in various biomedical applications, induces either DNA strand breaks or oxidative DNA damage in TH-1 cells after short-term (3 h and 24 h) exposure even at high concentrations (Sramkova et al 2019)

  • Based on the survival profile of INPs after 7 days of treatment, the concentration of 2.2 μg/ml was selected for subsequent whole-genome analyses

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Summary

Introduction

Inorganic nanoparticles (INPs) have been widely used for a plethora of biomedical applications due to their unique physicochemical properties (e.g., magnetic, thermal, optical, or antibacterial). Provide more accurate imaging, diagnosis, innovative strategies for disease therapy via multimodal surface functional modifications and offer advanced solutions for regenerative medicine (Bayda et al 2018). Integrating therapeutic and diagnostic properties in a single nanoscale platform (called theranostics) makes INPs an exciting tool in disease management. Gold nanoparticles (AuNPs) and magnetic iron oxide nanoparticles (NPs), mainly magnetite – ­Fe3O4NPs and maghemite – ­Fe2O3NPs, are promising contrast agents (e.g., magnetic resonance imaging, MRI, positron emission tomography, PET), heating mediators in hyperthermia-based cancer therapy, and nanovectors for targeted drug/gene delivery as well as molecular biosensors (Dadfar et al 2019; Singh et al 2018). Titanium dioxide NPs ­(TiO2NPs) are becoming an important component in regenerative medicine as reinforcement material or as coatings improving osseointegration for the implants and as emerging antimicrobial agents (Jafari et al 2020). Several INPs are currently being utilized in clinical practice, and many others are in clinical trials

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