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However, photoresponsive materials applied in fluid-filled oral cavities present challenges\u2014specifically, retaining them within cariogenic biofilms is difficult, and when such agents are carried away, it diminishes the effectiveness of phototherapy. . Additionally, the lack of targeting efficiency for cariogenic biofilms and on-demand release mechanisms results in decreased bioavailability, leading to unsatisfactory antibacterial efficacy and potential side effects. To address the dilemma, a hyaluronic acid (HA)\u2013based MXene\/CuS (MCH) bio-heterojunction is elaborated and activated by the cariogenic biofilm microenvironment to exert efficient sterilization and biofilm elimination effects for rescuing dental caries. In this intelligent system, HA initiates accurate anchors by targeting hyaluronidase (HAase) derived from the cariogenic biofilm microenvironment, and the encapsulated MXene\/CuS (MC) bio-heterojunction is released on demand as the HAase-triggered reaction intensifies within the biofilms. Under near-infrared (NIR) irradiation, the liberated MC is endowed with exceptional photosensitive attributes, simultaneously generating thermal energy and reactive oxygen species to perform synergistic photothermal and photodynamic therapy. In vitro results display that in cariogenic biofilms, the HA layer of MCH can react with HAase and undergo degradation, while maintaining a sufficient on-demand release of MC even under fluid rinsing. Subsequently, MCH and NIR irradiation combat bacteria and biofilm infection effectively through phototherapy physical mechanisms. Also, in vitro results demonstrate that oral cells perform normal extended morphology and considerable proliferation trends after MCH treatment. In addition, in vivo experiments authenticate that the MCH + NIR group shows excellent antibacterial efficacy, and micro\u2013computed tomography analysis and the modified Keyes score calculation indicate more intact enamel with no caries observed on rat molars. This pioneering approach heralds a promising avenue for the application of cariogenic biofilm microenvironment-activated photoresponsive materials in the domain of dental caries prevention and treatment.<\/jats:p>","DOI":"10.1177\/00220345251347918","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T06:38:06Z","timestamp":1752820686000},"page":"245-255","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Antibacterial Bio-heterojunctions Targeting Biofilm for Caries Treatment"],"prefix":"10.1177","volume":"105","author":[{"given":"J.","family":"Luo","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2701-5179","authenticated-orcid":false,"given":"J.","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7121-9817","authenticated-orcid":false,"given":"K.","family":"Liang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1039\/C3TA15446G"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0NR04540C"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.0c09454"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201803549"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202401795"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202310599"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202007778"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4MH00453A"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11070880"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202304324"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-019-0062-1"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202104448"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3TB00307H"},{"key":"e_1_3_3_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2021.12.016"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.121084"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.4c00671"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201601694"},{"key":"e_1_3_3_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c01913"},{"key":"e_1_3_3_20_1","doi-asserted-by":"publisher","DOI":"10.4103\/0970-4388.105016"},{"key":"e_1_3_3_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202105747"},{"key":"e_1_3_3_22_1","unstructured":"Parikh S. 1964. 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