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U.S.A."],"published-print":{"date-parts":[[2024,3,12]]},"abstract":"<jats:p>Autoimmune and inflammatory diseases are highly complex, limiting treatment and the development of new therapies. Recent work has shown that cell-free DNA bound to biological microparticles is linked to systemic lupus erythematosus, a prototypic autoimmune disease. However, the heterogeneity and technical challenges associated with the study of biological particles have hindered a mechanistic understanding of their role. Our goal was to develop a well-controlled DNA\u2013particle model system to understand how DNA\u2013particle complexes affect cells. We first characterized the adsorption of DNA on the surface of polystyrene nanoparticles (200 nm and 2 \u00b5m) using transmission electron microscopy, dynamic light scattering, and colorimetric DNA concentration assays. We found that DNA adsorbed on the surface of nanoparticles was resistant to degradation by DNase 1. Macrophage cells incubated with the DNA\u2013nanoparticle complexes had increased production of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-\u03b1) and interleukin 6 (IL-6). We probed two intracellular DNA sensing pathways, toll-like receptor 9 (TLR9) and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING), to determine how cells sense the DNA\u2013nanoparticle complexes. We found that the cGAS-STING pathway is the primary route for the interaction between DNA\u2013nanoparticles and macrophages. These studies provide a molecular and cellular-level understanding of DNA\u2013nanoparticle\u2013macrophage interactions. In addition, this work provides the mechanistic information necessary for future in vivo experiments to elucidate the role of DNA\u2013particle interactions in autoimmune diseases, providing a unique experimental framework to develop novel therapeutic approaches.<\/jats:p>","DOI":"10.1073\/pnas.2319634121","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T13:46:23Z","timestamp":1709646383000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":13,"title":["DNA corona on nanoparticles leads to an enhanced immunostimulatory effect with implications for autoimmune diseases"],"prefix":"10.1073","volume":"121","author":[{"given":"Faisal","family":"Anees","sequence":"first","affiliation":[{"name":"Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 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