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Using nanoparticles to invade biofilms and produce reactive oxygen species (ROS) in situ is a promising strategy for killing bacteria and disrupting the structure of biofilms. In this work, a biofilm\u2010targeting Fenton nanoreactor is reported that can generate ROS responsive to the cariogenic microenvironment. The nanoreactor is constructed by metal\u2010phenolic encapsulation of calcium peroxide (CaO<jats:sub>2<\/jats:sub>) followed by modification with a biofilm targeting ligand dextran. Within the cariogenic biofilm, the Fenton nanoreactor is activated by an acidic microenvironment to be decomposed into H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> and iron ions, triggering a Fenton\u2010like reaction to generate ROS that can eliminate the biofilm by breaking down extracellular polymeric substances\u00a0(EPS)\u00a0and killing cariogenic bacteria. Meanwhile, the depletion of excess protons in biofilm leads to a reversal of the cariogenic microenvironment. The Fenton nanoreactor can effectively inhibit the biofilm formation of <jats:italic>Streptococcus mutans<\/jats:italic> on ex vivo human teeth and is effective in preventing caries meanwhile maintaining the oral microbial diversity in rat caries infection model. This work provides a novel and efficient modality for acid microenvironment\u2010driven ROS therapy.<\/jats:p>","DOI":"10.1002\/adhm.202303466","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T09:13:29Z","timestamp":1700558009000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Microenvironment\u2010Driven Fenton Nanoreactor Enabled by Metal\u2010Phenolic Encapsulation of Calcium Peroxide for Effective Control of Dental Caries"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiaoru","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Biomaterials School and Hospital of Stomatology Cheeloo College of Medicine Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases  Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlong","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Periodontology School and Hospital of Stomatology Cheeloo College of Medicine Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases  Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yandi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biomaterials School and Hospital of Stomatology Cheeloo College of Medicine Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases  Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Debtistry School and Hospital of Stomatology Cheeloo College of Medicine Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases  Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohua","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Periodontology School and Hospital of Stomatology Cheeloo College of Medicine Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases  Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5227-8627","authenticated-orcid":false,"given":"Jianhua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomaterials School and Hospital of Stomatology Cheeloo College of Medicine Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases  Jinan Shandong 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,28]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.30"},{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2017.09.008"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/mr.50.4.353-380.1986"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2015.00010"},{"key":"e_1_2_8_2_3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1919099117"},{"key":"e_1_2_8_2_4","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.895537"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-5712(10)70005-1"},{"key":"e_1_2_8_3_2","first-page":"1103","volume":"18","author":"He Y.","year":"2014","journal-title":"Clin. 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