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Herein, the authors have developed nanogels (NGs) to destroy both planktonic bacteria and SCVs and eliminate excessive inflammations for peritonitis and sepsis therapies. Free gentamicin (GEN) and hydroxyapatite nanoparticles (NPs) with GEN loading and mannose grafts (mHA<jats:sub>G<\/jats:sub>) are inoculated into \u03b5\u2010polylysine NGs to obtain NG@G1\u2010mHA<jats:sub>G2<\/jats:sub> through crosslinking with phenylboronic acid and tannic acid. The H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> consumption after reaction with phenylboronic esters and the elimination of free radicals by tannic acid alleviates the escalated inflammatory status to promote sepsis therapy. After mannose\u2010mediated uptake into macrophages, the acid\u2010triggered degradation of mHA<jats:sub>G<\/jats:sub> NPs generates Ca<jats:sup>2+<\/jats:sup> to destabilize lysosomes and the efficient lysosomal escape leads to reversion of hypometabolic SCVs into normal phenotype and their sensitivity to GEN. In a peritonitis mouse model, NG@G1\u2010mHA<jats:sub>G2<\/jats:sub> treatment provides strong and persistent bactericidal effects against both extracellular bacteria and intracellular SCVs and extends survival of peritonitis mice without apparent hepatomegaly, splenomegaly, pulmonary edema, and inflammatory cell infiltration. Thus, this study demonstrates a concise and versatile strategy to eliminate SCVs and relieve inflammatory storms for peritonitis and sepsis therapies without infection recurrence.<\/jats:p>","DOI":"10.1002\/adhm.202303671","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T13:24:25Z","timestamp":1709126665000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Dual\u2010Responsive Nanogels with Cascaded Gentamicin Release and Lysosomal Escape to Combat Intracellular Small Colony Variants for Peritonitis and Sepsis Therapies"],"prefix":"10.1002","volume":"13","author":[{"given":"Shuang","family":"Xie","sequence":"first","affiliation":[{"name":"School of Life Science and Engineering Key Laboratory of Advanced Technologies of Materials Ministry of Education Southwest Jiaotong University  Chengdu 610031 P. R. 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