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To fight against bacterium\u2010induced drug resistance, herein we design self\u2010traceable nanoreservoirs that are simultaneously loaded with gemcitabine (an anticancer drug) and ciprofloxacin (an antibiotic) and are decorated with hyaluronic acid for active tumor targeting. The nanoreservoirs have a pH\u2010sensitive gate and an enzyme\u2010responsive gate that can be opened in the acidic and hyaluronidase\u2010abundant tumor microenvironment to control drug release rates. Moreover, the nanoreservoirs can specifically target the tumor regions without eliciting evident toxicity to normal tissues, kill the intratumoral bacteria, and inhibit the tumor growth even in the presence of the bacteria. Unexpectedly, the nanoreservoirs can activate T cell\u2010mediated immune responses through promoting antigen\u2010presenting dendritic cell maturation and depleting immunosuppressive myeloid\u2010derived suppressor cells in bacterium\u2010infected tumors.<\/jats:p>","DOI":"10.1002\/anie.202102059","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T04:44:54Z","timestamp":1616733894000},"page":"14013-14021","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Dual Gate\u2010Controlled Therapeutics for Overcoming Bacterium\u2010Induced Drug Resistance and Potentiating Cancer Immunotherapy"],"prefix":"10.1002","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4137-3535","authenticated-orcid":false,"given":"Xiaodong","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioelectronics School of Biological Science and Medical Engineering 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