Minireview: Nanoparticles and the Immune System

Center for Drug Evaluation and Research, Office of Pharmaceutical Science, Food and Drug Administration, Silver Spring, Maryland 20993, USA.
Endocrinology (Impact Factor: 4.5). 12/2009; 151(2):458-65. DOI: 10.1210/en.2009-1082
Source: PubMed


Today nanotechnology is finding growing applications in industry, biology, and medicine. The clear benefits of using nanosized products in various biological and medical applications are often challenged by concerns about the lack of adequate data regarding their toxicity. One area of interest involves the interactions between nanoparticles and the components of the immune system. Nanoparticles can be engineered to either avoid immune system recognition or specifically inhibit or enhance the immune responses. We review herein reported observations on nanoparticle-mediated immunostimulation and immunosuppression, focusing on possible theories regarding how manipulation of particle physicochemical properties can influence their interaction with immune cells to attain desirable immunomodulation and avoid undesirable immunotoxicity.

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    • "In humans, NPs are first recognized by the cells of the immune system (e.g. monocytes) and their undesirable interactions may lead to immunostimulation or immunosuppression, inflammatory or autoimmune disorders, infections and cancer (Zolnik et al., 2010). Immune system can even engulf and eliminate certain NPs (Dobrovolskaia et al., 2008). "
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    ABSTRACT: The wide application of zinc oxide nanoparticles (ZnO NPs) in cosmetics, paints, biosensors, drug delivery, food packaging and as anticancerous agents has increased the risk of human exposure to these NPs. Earlier in vitro and in vivo studies have demonstrated a cytotoxic and genotoxic potential of ZnO NPs. However, there is paucity of data regarding their immunomodulatory effects. Therefore, the present study was aimed to investigate the immunotoxic potential of ZnO NPs using human monocytic cell line (THP-1) as model to understand the underlying molecular mechanism. A significant (p < 0.01) increase in pro-inflammatory cytokines (TNF-α and IL-1β) and reactive oxygen species (ROS) was observed with a concomitant concentration dependent (0.5, 1, 5, 10, 15 and 20 μg/mL) decrease in the glutathione (GSH) levels as compared to control. The expression levels of mitogen activated protein kinase (MAPK) cascade proteins such as p-ERK1/2, p-p38 and p-JNK were also significantly (p < 0.05, p < 0.01) induced. Also, at the concentration tested, NPs induced DNA damage as assessed by the Comet and micronucleus assays. Our data demonstrated that ZnO NPs induce oxidative and nitrosative stress in human monocytes, leading to increased inflammatory response via activation of redox sensitive NF-κB and MAPK signalling pathways. Copyright © 2015. Published by Elsevier Ltd.
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    • "Similar results were described in the work ofKorani et al., 2011, who mentioned that longgterm skin conn tact with colloid nanosilver (in a concentration of 100, 1000 and 10000 μkg/mL) led to the development of an inflammatory reaction in the liver and spleen of mice and rats and carried a doseeindependent character[7]. The immunotoxicity of nanoparticles also appears in the ability to stimulate the production of cytokines[19]. Park et al., 2010, showed a doseedependent increment of antiiinflammatory and proinflammatory cytokines content, including IFNNγ in the blood serum of mice after the peroral administration of silver nanoparticles with a size of 42 nm in doses: 0.25 mg/kg, 0.5 mg/kg and 1 mg/kg in 28 days[12]. The induction of cytokines is strongly influenced by the physicochemical peculiarities of the nanoparticle surface. "
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    ABSTRACT: In this study we have identified the influence of Argovit on the immune system of mice after inhalation or intragastric or subcutaneous administration. Argovit is a preparation of polyvinylpyrrolidone-coated (43.6 ± 10.7 nm) silver nanoparticles. We have found no toxic effect on the immune cells and organs, changes in T- and B-lymphocytes quantity in the spleen, or proinflammatory cytokine production after exposure to silver nanoparticles through inhalation or intragastrically. The subcutaneous administration of silver nanoparticles has changed the ratio of lymphocyte subpopulations, increased the quantity of IFN-γ-producing T-lymphocytes 3.6-fold compared with the control, and increased the content of IFN-γ in the serum of mice to 125 ± 9.2 pg/mL compared to the control (74.5 ± 6.4 pg/mL).
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    • "The physico-chemical properties of NPs have proved to play an essential role in the modulation of DC immune responses during maturation, T lymphocyte proliferation and cytokine secretion. NP type [8] [18], size [29e32], shape [33], surface charge [34] and hydrophobicity [35] strongly affect the inflammatory responses of DCs and the level of cytotoxicity [29] [36]. For instance, several in vitro and in vivo studies with polymeric and metallic NPs suggest that a size lower than 200 nm enhances DC uptake, improves immunoresponse induction and the delivery of antigens [27] [30]. "
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    ABSTRACT: We have studied the effect of highly fluorescent gold nanoclusters (Au NCs) (∅< 3nm) stabilized by different ligands on the intracellular accumulation and immune response of human derived-monocyte dendritic cells (DCs). Results indicate that the high uptake efficiency of Au NCs is strongly related to their small size and to the nature of the ligand, with zwitterionic ligands being more effective than pegylated ones. Evidence from flow cytometry and microscopy demonstrate time and concentration-dependent Au NCs internalization by endocytic pathway(s) involving amorphous and laminar organelles, while maintaining their discrete size and photoluminescence properties. The uptake of zwitterionic ligand-stabilized Au NCs induced very low cytotoxicity and a strong immunosuppressive response (Th1/Treg pattern), associated with a DC maturation state. This behavior contrasts to the effect of bigger particles (∼12nm size) which induced a cytotoxic response involving Natural Killer (CD56) cells. Overall, this study stresses the critical importance of particle size and ligand type on the immunostimulation of DCs and highlights the remarkable potential of this new class of nanomaterial as a novel vaccine platform.
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