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Despite various treatments, cariogenic bacteria persist, resulting in a pessimistic outlook for the prevention and treatment of ECC. A notable presence of persister cells is found within the cariogenic bacterial population, with their dormancy enabling them to evade antiseptics. Mechanistically, the downregulation of heat shock proteins (HSPs) leads to protein aggresome formation, converting active cariogenic bacteria into persisters, which confers dual defensive barriers through metabolic inertness and concomitant reduction of membrane permeability, rendering conventional antimicrobials ineffective. Given these findings, Ti\n                    <jats:sub>3<\/jats:sub>\n                    C\n                    <jats:sub>2<\/jats:sub>\n                    MXene, a 2D nanomaterial acting as a \u201cnanothermal knife\u201d to disrupt persister cell membranes is developed. Ti\n                    <jats:sub>3<\/jats:sub>\n                    C\n                    <jats:sub>2<\/jats:sub>\n                    \u2010mediated photothermal therapy (PTT) upregulated HSPs, inhibited aggresome formation, and prevented persister dormancy, showing efficacy against planktonic and biofilm cariogenic persisters. This PTT strategy demonstrates remarkable efficacy against planktonic cariogenic persisters and multispecies biofilms. Furthermore, the in vivo establishment of aggressive caries models reveals a substantial reduction of cariogenic pathogens following combined Ti\n                    <jats:sub>3<\/jats:sub>\n                    C\n                    <jats:sub>2<\/jats:sub>\n                    \u2010mediated PTT and antimicrobial treatment, effectively suppressing caries progression. This light\u2010assisted antibacterial strategy may aid ECC prevention.\n                  <\/jats:p>","DOI":"10.1002\/advs.202501501","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T07:08:57Z","timestamp":1749539337000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A MXene\u2010Based Nanothermal Knife Inhibits Aggresome\u2010Mediated Persister Formation for Preventing Dental Caries"],"prefix":"10.1002","volume":"12","author":[{"given":"Yinyin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Stomatology The First Affiliated Hospital of Zhengzhou University  Zhengzhou 45000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leilei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Stomatology The First Affiliated Hospital of Zhengzhou University  Zhengzhou 45000 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