Nanoparticle treatment inhibits macrophage polarization towards the anti-inflammatory M2 subset

• Published in: European journal of cancer (1990) Vol. 69; p. S69
• Main Authors: Fuchs, A.K, Syrovets, T, Loos, C, Haas, K, Simmet, T
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Science Ltd 01.12.2016
• Subjects: Biocompatibility; Biomedical materials; CD163 antigen; Disease control; Exposure; Hematology, Oncology and Palliative Medicine; Human body; Immune response; Immune system; Immunology; Immunosuppression; Inflammation; Innate immunity; Interleukin 10; Macrophages; Monocytes; Nanomaterials; Nanoparticles; Nanotechnology; Peripheral blood; Phenotypes; Polarization; Polystyrene; Polystyrene resins; Proteins; Solid tumors; Surface charge; Toxicity
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/S0959-8049(16)32794-0

Background: In the last few years, nanomaterials moved into focus of biomedical research partly for toxicological reasons, but increasingly also for their potential application in therapy and diagnosis. In spite of their potential medical use, nanomaterials might induce non-specific "adverse effects" in the human body. Macrophages play an important role in the immunological defense of the human body. Because they guard all entry sites of the body including the circulation, macrophages are among the first cells to encounter infiltrating nanoparticles. Yet macrophages may differentiate into distinct subsets exerting a variety of diverse tasks, which range for example from proinflammatory (M1 subset) to immunosuppressive (M2 subset, e.g. in solid tumors) functions. The aim of this study was to investigate the effects of positively and negatively charged nanoparticles on the so-called macrophage polarization. Material and Methods: Human peripheral blood monocytes were differentiated in vitro into M1 and M2 macrophages and the impact of amino or carboxyl functionalized polystyrene nanoparticle exposure on cell viability and polarization profiles was investigated. Proinflammatory M1 and anti-inflammatory M2 macrophage subtypes were characterized by morphology, protein markers, cytokine secretion profiles and functional differences. Results: In vitro differentiated M1 and M2 macrophages took up, both, positively and negatively charged polystyrene nanoparticles. Viability was not compromised by nanoparticle exposure for 3 days; however, negatively charged nanoparticles increased the metabolic activity of both macrophage subsets. Regardless of the surface charge, nanoparticles inhibited polarization towards anti-inflammatory M2 macrophages as seen by decreased expression of CD163 and CD200R, and inhibition of IL-10 secretion. Conclusions: Despite intensive investigations of nanomaterials for biomedical applications, there are still important unresolved questions regarding their toxicity that need to be addressed. In our study we found that nanoparticles greatly inhibit macrophage polarization towards the M2 phenotype. As part of the innate immune system, macrophages strongly control inflammatory processes. Dysregulation of macrophage polarization might lead to disease states, however, controlled manipulation of M1 and M2 macrophage polarization could also be exploited to shape immune responses.