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Currently, the drugs under development only target a single pathogenesis, which is obviously insufficient. In this study, an acid\u2010responsive hollow mesoporous polydopamine (HMPDA) nanocarrier that is highly capable of carrying both the hydrophilic drug NAD\n                    <jats:sup>+<\/jats:sup>\n                    and the hydrophobic drug BAPTA\u2010AM, with its outer layer being sealed by the inflammatory targeting peptide PEG\u2010LSA, is developed. Once targeted to the region of inflammation, HMPDA begins depolymerization, releasing the drugs NAD\n                    <jats:sup>+<\/jats:sup>\n                    and BAPTA\u2010AM. Depletion of polydopamine on excessive reactive oxygen species production, promotion of ATP production and anti\u2010inflammation by NAD\n                    <jats:sup>+<\/jats:sup>\n                    replenishment, and chelation of BAPTA (generated by BA\u2010AM hydrolysis) on overloaded Ca\n                    <jats:sup>2+<\/jats:sup>\n                    can comprehensively block the three stages of sepsis, i.e., precisely inhibit the activation of pyroptosis pathway (NF\u2010\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B\u2010NLRP3\u2010ASC\u2010Casp\u20101), inflammation pathway (IL\u20101\n                    <jats:italic>\u03b2<\/jats:italic>\n                    , IL\u20106, and TNF\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    ), and mitochondrial apoptosis pathway (Bcl\u20102\/Bax\u2010Cyt\u2010C\u2010Casp\u20109\u2010Casp\u20103), thereby restoring intracellular homeostasis, saving the cells in a state of \u201ccritical survival,\u201d further reducing LPS\u2010induced systemic inflammation, finally restoring the organ functions. In conclusion, the synthesis of this agent provides a simple and effective synergistic drug delivery nanosystem, which demonstrates significant therapeutic potential in a model of LPS\u2010induced sepsis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202207448","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T23:45:35Z","timestamp":1679096735000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Rapidly Inhibiting the Inflammatory Cytokine Storms and Restoring Cellular Homeostasis to Alleviate Sepsis by Blocking Pyroptosis and Mitochondrial Apoptosis Pathways"],"prefix":"10.1002","volume":"10","author":[{"given":"Jiahui","family":"Yan","sequence":"first","affiliation":[{"name":"Frontiers Science Center for Deep Ocean Multispheres and Earth System and Key Laboratory of Marine Chemistry Theory and Technology Ministry of Education Ocean University of China  Qingdao 266100 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