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Despite discoveries of many potential therapeutic targets, effective treatments of sepsis are lacking. Here, a strategy is reported to target infectious microenvironments (IMEs) via bioresponsive nanoparticles that simultaneously eliminate bacteria and alleviate the host inflammation response, thus managing sepsis in mice. The nanoparticle is made of copolymers sensitive to pH and bacterial enzymes to self\u2010assemble into a micelle loaded with both an antibiotic (ciprofloxacin) and an anti\u2010inflammatory agent ((2\u2010[(aminocarbonyl)amino]\u20105\u2010(4\u2010fluorophenyl)\u20103\u2010thiophenecarboxamide). In addition, the nanoparticle is conjugated with intercellular adhesion molecule\u20101 antibodies to target IMEs. Nanoparticle targeting to IMEs and local cues as triggers to deliver therapeutics in on\u2010demand manners is demonstrated using an acute lung bacterial infection mouse model. In the sepsis mouse model induced by peritonitis at a lethal dose of bacterial invasion, it is shown that concurrently targeting pathogens and excessive inflammation pathways is valuable to manage the sepsis. The study illustrates not only the development of a new delivery system but also the mechanism\u2010based therapy of nanomedicine for infectious diseases.<\/jats:p>","DOI":"10.1002\/adma.201803618","type":"journal-article","created":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T04:01:50Z","timestamp":1536638510000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":199,"title":["Bioresponsive Nanoparticles Targeted to Infectious Microenvironments for Sepsis Management"],"prefix":"10.1002","volume":"30","author":[{"given":"Can Yang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy and Pharmaceutical Sciences Washington State University  Spokane WA 99210 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy and 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