{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T06:07:23Z","timestamp":1783836443382,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["cstc2021jcyj\u2010msxmX1179"],"award-info":[{"award-number":["cstc2021jcyj\u2010msxmX1179"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Severe lung inflammation and acute respiratory distress syndrome (ARDS) represent one of the most life\u2010threatening conditions in critical care units and no effective drugs are available clinically. Here, we show that the polymerization of arginine greatly boosts the anti\u2010inflammatory effect of arginine in vitro. RNA transcription sequencing and analysis indicated that polyarginine upregulated the expression of the anti\u2010inflammatory cytokine IL\u20104. Meanwhile, polyarginine can assemble DNA nanostructures in a magnesium\u2010free manner and enhance the cellular uptake of DNA due to its cell\u2010penetrating nature, thereby boosting DNA nanostructure\u2010based drug delivery efficiency. To validate the potential of polyarginine as an anti\u2010inflammation prodrug, an arginine trimer (3R) assembled DNA nanotube that carries p65 siRNA (NT\n                    <jats:sup>3R<\/jats:sup>\n                    \u2010p65) was assembled as a model nanomedicine for ARDS therapy. Flow cytometry results showed polyarginine\u2010assembled DNA nanotubes exhibited higher cellular uptake efficiencies than the magnesium\u2010assembled counterpart. Most importantly, NT\n                    <jats:sup>3R<\/jats:sup>\n                    \u2010p65 effectively suppressed lung inflammatory in vitro and in ARDS mouse models. Mechanistically, 3R suppresses phosphorylated p65 expression and upregulates IL\u20104 signaling pathway while p65 siRNA directly silencing p65 expression. The prodrug 3R and p65 siRNA exhibited additive anti\u2010inflammation effects in vitro and vivo. Collectively, the prodrug and gene therapy combination might offer a potential strategy for treating ARDS or other severe lung inflammation\u2010related diseases.\n                  <\/jats:p>","DOI":"10.1002\/smll.202511807","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T09:00:43Z","timestamp":1768381243000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Arginine Polymerization Boosts Anti\u2010Inflammatory Effects and DNA Nanostructure\u2010Assisted siRNA Delivery in Acute Respiratory Distress Syndrome"],"prefix":"10.1002","volume":"22","author":[{"given":"Boxuan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Xinqiao Hospital of Third Military Medical University (Army Medical University) Chongqing China"},{"name":"Department of Pharmacy Changzhi Medical College  Changzhi Shanxi 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