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Our previous studies have found that tetrahedral framework nucleic acid (tFNA) plays a mild anti\u2010inflammatory effect by inhibiting macrophage activation, but the specific mechanism remains unclear. Here, by metabolomics and RNA sequencing, choline uptake is identified to be significantly repressed by decreased <jats:italic>slc44a1<\/jats:italic> expression in tFNA\u2010treated activated macrophages. Inspired by this result, combined with the excellent delivery capacities of tFNA, siR\u2010slc44a1 is loaded into the tFNA to develop a new tFNA\u2010based small interfering RNA (siRNA) delivery system named \u2018nano\u2010windmill,\u2019 which exhibits a synergetic role by targeting <jats:italic>slc44a1<\/jats:italic>, finally blowing up the anti\u2010inflammatory effects of tFNA to inhibit macrophages activation via reducing choline uptake. By confirming its anti\u2010inflammatory effects in chronic (periodontitis) and acute (sepsis) inflammatory disease, the tFNA\u2010based nanomedicine developed for inflammatory diseases may provide broad prospects for tFNA upgrading and various biological applications such as anti\u2010inflammatory.<\/jats:p>","DOI":"10.1111\/cpr.13470","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T09:16:50Z","timestamp":1681377410000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The nano\u2010windmill exerts superior anti\u2010inflammatory effects via reducing choline uptake to inhibit macrophage activation"],"prefix":"10.1111","volume":"56","author":[{"given":"Nanxin","family":"Liu","sequence":"first","affiliation":[{"name":"Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education  Chongqing P. 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