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Lipid nanoparticles (LNPs) serve as an effective vehicle for delivering small interfering ribonucleic acids (siRNA) that represent a method to knockdown integrin \u03b15\u03b21 in the lungs through nebulization, thereby potentially mitigating the severity of\n                      <jats:italic>S. aureus<\/jats:italic>\n                      pneumonia. The aim of this study was to harness LNP-mediated targeting to precisely knockdown integrin \u03b15\u03b21, thus effectively addressing\n                      <jats:italic>S. aureus<\/jats:italic>\n                      -induced pneumonia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      C57 mice (8\u00a0week-old females) infected with\n                      <jats:italic>S. aureus<\/jats:italic>\n                      via an intratracheal nebulizing device were utilized for the experiments. The LNPs were synthesized via microfluidic mixing and characterized by their size, polydispersity index, and encapsulation efficiency. Continuous intratracheal nebulization was employed for consistent siRNA administration, with the pulmonary function metrics affirming biosafety. The therapeutic efficacy of LNP-encapsulated siRNAs against pneumonia was assessed through western blotting, bacterial count measurement, quantitative polymerase chain reaction, and histological analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      LNPs, which have an onion-like structure, retained integrity post-nebulization, ensuring prolonged siRNA stability and in vivo safety. Intratracheal nebulization delivery markedly alleviated the severity of\n                      <jats:italic>S. aureus<\/jats:italic>\n                      -induced pneumonia, as indicated by reduced bacterial load and bolstered immune response, thereby localizing the infection to the lungs and averting systemic dissemination.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Intratracheal nebulization of LNP-encapsulated siRNAs targeting integrin \u03b15\u03b21 significantly diminished the\n                      <jats:italic>S. aureus<\/jats:italic>\n                      -mediated cellular invasion and disease progression in the lungs, presenting a viable therapeutic approach for respiratory infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-024-05711-9","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T16:23:45Z","timestamp":1729009425000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Innovative nebulization delivery of lipid nanoparticle-encapsulated siRNA: a therapeutic advance for Staphylococcus aureus-induced pneumonia"],"prefix":"10.1186","volume":"22","author":[{"given":"Meiqi","family":"Meng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiachao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongru","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bai","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9021-7040","authenticated-orcid":false,"given":"Cuiqing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"issue":"7","key":"5711_CR1","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1038\/s41591-019-0468-5","volume":"25","author":"FA Vieira Braga","year":"2019","unstructured":"Vieira Braga FA, Kar G, Berg M, et al. 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