INTRODUCTION: A critical step preceding the potential biomedical application of nanoparticles is the evaluation of their immunomodulatory effects. Such nanoparticles are expected to enter the bloodstream where they can be recognized and processed by circulating monocytes. Despite the required biocompatibility, this interaction can affect intracellular homeostasis and modulate physiological functions, particularly inflammation. This study focuses on titanium dioxide (TiO2) as an example of relatively low cytotoxic nanoparticles with potential biomedical use and aims to evaluate their possible modulatory effects on the inflammasome-based response in human primary monocytes. METHODS: Monocyte viability, phenotypic changes, and cytokine production were determined after exposure to TiO2 (diameter, 25 nm; P25) alone. In the case of the modulatory effects, we focused on NLRP3 activation. The production of IL-1β and IL-10 was evaluated after (a) simultaneous activation of monocytes with bacterial stimuli muramyl dipeptide (MDP), or lipopolysaccharide (LPS), and TiO2 (co-exposure model), (b) prior activation with TiO2 alone and subsequent exposure to bacterial stimuli MDP or LPS. The differentiation of TiO2-treated monocytes into macrophages and their polarization were also assessed. RESULTS: The selected TiO2 concentration range (30-120 µg/mL) did not induce any significant cytotoxic effects. The highest dose of TiO2 promoted monocyte survival and differentiation into macrophages, with the M2 subset being the most prevalent. Nanoparticles alone did not induce substantial production of inflammatory cytokines IL-1β, IL-6, or TNF-α. The immunomodulatory effect on NLRP3 depended on the type of costimulant used. While co-exposure of monocytes to MDP and TiO2 boosted NLRP3 activity, co-exposure to LPS and TiO2 inhibited NLRP3 by enhancing IL-10 release. The inhibitory effect of TiO2 on NLRP3 based on the promotion of IL-10 was confirmed in a post-exposure model for both costimulants. CONCLUSION: This study confirmed a non-negligible modulatory effect on primary monocytes in their inflammasome-based response and differentiation ability.

• Keywords
• NLRP3, TiO2 nanoparticles, immunomodulation, macrophages, monocytes, polarization,
• MeSH
• Acetylmuramyl-Alanyl-Isoglutamine pharmacology   MeSH
• Cell Differentiation drug effects   MeSH
• Cytokines metabolism   MeSH
• Inflammasomes drug effects   immunology   metabolism   MeSH
• Interleukin-10 metabolism   MeSH
• Interleukin-1beta metabolism   MeSH
• Metal Nanoparticles * toxicity   chemistry   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Lipopolysaccharides pharmacology   MeSH
• Macrophages drug effects   immunology   MeSH
• Monocytes * drug effects   immunology   cytology   MeSH
• Nanoparticles * toxicity   chemistry   MeSH
• NLR Family, Pyrin Domain-Containing 3 Protein metabolism   MeSH
• Toxicity Tests methods   MeSH
• Titanium * toxicity   chemistry   pharmacology   MeSH
• Cell Survival drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Acetylmuramyl-Alanyl-Isoglutamine MeSH
• Cytokines MeSH
• Inflammasomes MeSH
• Interleukin-10 MeSH
• Interleukin-1beta MeSH
• Lipopolysaccharides MeSH
• NLRP3 protein, human MeSH Browser
• NLR Family, Pyrin Domain-Containing 3 Protein MeSH
• Titanium * MeSH
• titanium dioxide MeSH Browser

In the field of science, technology and medicine, carbon-based nanomaterials and nanoparticles (CNMs) are becoming attractive nanomaterials that are increasingly used. However, it is important to acknowledge the risk of nanotoxicity that comes with the widespread use of CNMs. CNMs can enter the body via inhalation, ingestion, intravenously or by any other route, spread through the bloodstream and penetrate tissues where (in both compartments) they interact with components of the immune system. Like invading pathogens, CNMs can be recognized by large numbers of receptors that are present on the surface of innate immune cells, notably monocytes and macrophages. Depending on the physicochemical properties of CNMs, i.e., shape, size, or adsorbed contamination, phagocytes try to engulf and process CNMs, which might induce pro/anti-inflammatory response or lead to modulation and disruption of basic immune activity. This review focuses on existing data on the immunotoxic potential of CNMs, particularly in professional phagocytes, as they play a central role in processing and eliminating foreign particles. The results of immunotoxic studies are also described in the context of the entry routes, impacts of contamination and means of possible elimination. Mechanisms of proinflammatory effect depending on endocytosis and intracellular distribution of CNMs are highlighted as well.

• Keywords
• carbon nanotubes, carbon-based nanomaterials, graphene, immunomodulation, immunotoxicity, inflammasome, macrophages, monocytes,
• MeSH
• Macrophages MeSH
• Nanostructures * chemistry   toxicity   MeSH
• Carbon * chemistry   MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Carbon * MeSH

Graphene and its derivatives are popular nanomaterials used worldwide in many technical fields and biomedical applications. Due to such massive use, their anticipated accumulation in the environment is inevitable, with a largely unknown chronic influence on living organisms. Although repeatedly tested in chronic in vivo studies, long-term cell culture experiments that explain the biological response to these nanomaterials are still scarce. In this study, we sought to evaluate the biological responses of established model A549 tumor cells exposed to a non-toxic dose of pristine graphene for eight weeks. Our results demonstrate that the viability of the A549 cells exposed to the tested graphene did not change as well as the rate of their growth and proliferation despite nanoplatelet accumulation inside the cells. In addition, while the enzymatic activity of mitochondrial dehydrogenases moderately increased in exposed cells, their overall mitochondrial damage along with energy production changes was also not detected. Conversely, chronic accumulation of graphene nanoplates in exposed cells was detected, as evidenced by electron microscopy associated with impaired cellular motility.

• Keywords
• cell migration, graphene accumulation, in vitro, long-term cultivation, mitochondrial metabolism, nanomaterials, pristine graphene, toxicity,
• Publication type
• Journal Article MeSH

Graphene-based nanomaterials received attention from scientists due to their unique properties: they are highly conductive, mechanically resistant and elastic. These materials can be used in different sectors of society from electronic energy storage in industry to biomedical applications. This study evaluates the influence of graphene nanoplatelets in vitro and in vivo. The toxicological influence of graphene nanoplatelets (GPs) was analyzed by cytotoxic methods, the change of cell proliferation was assessed in real-time, and the effect of GPs on a living organism was evaluated in an animal model using histopathological examination. We analyzed two types of GP administration: intratracheal and peroral. We found dose- and time-dependent cytotoxic effects of GPs in vitro; the concentration above 50 μg/mL increased the cytotoxicity significantly. The real-time analysis confirmed these data; the cells exposed to a high concentration of GPs for a longer time period resulted in a decrease in cell index which indicated lower cell viability. Histopathological examination revealed thickened alveolar septa and accumulation of GPs in the endocardium after intratracheal exposure. Peroral administration did not reveal any morphological changes. This study showed the dose- and time-dependent cytotoxic potential of graphene nanoplatelets in in vitro and in vivo models.

• Keywords
• C57Bl/6 mice, PAECs, cytotoxicity, graphene nanoplatelets, nanomaterials,
• Publication type
• Journal Article MeSH