A MXene-Based Nanothermal Knife Inhibits Aggresome-Mediated Persister Formation for Preventing Dental Caries

Early childhood caries (ECC) is one of the most common chronic diseases among children globally, affecting the health and quality of life of children. 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, Ti₃C₂ MXene, a 2D nanomaterial acting as a "nanothermal knife" to disrupt persister cell membranes is developed. Ti₃C₂-mediated 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 Ti₃C₂-mediated PTT and antimicrobial treatment, effectively suppressing caries progression. This light-assisted antibacterial strategy may aid ECC prevention.