Nanoparticles and nanomaterials are defined as a substances with at least one dimension less than 100 nm in size. Due to their high surface area and small volume, coupled to other physicochemical properties, nanoparticles have interesting but sometimes unexpected properties substantially different from the bulk materials of the same composition. The ever-increasing development of nanoparticles with various physicochemical properties for different industrial applications has greatly enhanced human exposure to nanomaterials. The aim of the project is to test the hypothesis predicting that nanoparticles widely used in medicine and industry may interfere with the cellular signaling activated by the tumor necrosis factor (TNF, formerly known as TNFα). Such interference may change the final cellular result of TNF action and disrupt the cellular homeostasis contributing to the development of malignancies, such as cancer or autoimmune diseases.
In the project we plan to exploit two cellular models, namely hepatic HepG2 and lung epithelial A549 cell lines to study the impact of nanoparticles on TNF-related signaling pathways. We will study three types of nanoparticles (approx. 20 nm in size) widely used in medicine and industry: (1) Gold nanoparticles used for diagnostic and therapeutic purposes, including targeted delivery of anticancer drugs, bioimaging of cells and tissues, contrast agents and radio-sensitizers; (2) Iron oxide nanoparticles used for in vivo applications, such as MRI contrast enhancement and drug delivery; (3) Silver nanopartciles that are widely used due to their antibacterial properties which makes them desirable additive to many products such as textiles, cosmetics, food packaging, surgical instruments or wound dressings. The influence of nanoparticles on TNF signaling will be studied by: analysis of cells viability, analysis of the expression of genes related to inflammatory response and cell death, analysis of epigenetic changes (DNA methylation, miRNA expression), analysis of NF-κB and MAPK signaling pathways activity.
The project will bring new knowledge concerning the effects of nanomaterials on cellular signal transduction networks and will reveal important information about the nature and specificity of the functional interactions between nanomaterials and cells. This knowledge will facilitate the purposeful design of nanomaterials and lay the foundation for the controlled manipulation of biological systems through nanotechnology.