{"title":"A novel pH-responsive monomer inhibits Candida albicans via a dual antifungal mode of action","authors":"Hao Li, Yangyang Shi, Hui Chen, Jingou Liang, Shiyong Zhang, Bolei Li, Jing Chen, Mingyun Li, Xian Peng, Xuedong Zhou, Biao Ren, Lei Cheng","doi":"10.1039/d4tb00851k","DOIUrl":null,"url":null,"abstract":"The scarcity of the antifungal drug arsenal highlights an urgent need to develop alternative treatments for candidiasis caused by <em>Candida albicans</em> (<em>C. albicans</em>). As pH is closely associated with <em>C. albicans</em> infection, it could be an essential target in a novel approach for designing antifungal therapy. In this study, a novel intelligent antifungal monomer, dodecylmethylaminoethyl methacrylate (DMAEM), with a pH-responsive tertiary amine group and a methacrylate-derived C<img alt=\"[double bond, length as m-dash]\" border=\"0\" src=\"https://www.rsc.org/images/entities/char_e001.gif\"/>C double bond group is developed. It is uncovered that the two functional groups of DMAEM contribute to a dual mode of action. Under acidic pH, the tertiary amine of DMAEM protonates into a cationic fungicide, sharing similar structural and functional characteristics with quaternary ammonium salts, which exerts fungicidal activity by targeting the <em>CHK1</em> two-component system in <em>C. albicans</em>. At neutral pH, the methacrylate-derived C<img alt=\"[double bond, length as m-dash]\" border=\"0\" src=\"https://www.rsc.org/images/entities/char_e001.gif\"/>C double bond group contributes to anti-virulence activity by blocking hyphal formation. In addition, it is also identified that DMAEM suppresses filamentation by altering the extracellular vesicles of <em>C. albicans</em>. These findings support that the novel intelligent pH-responsive monomer could be a therapeutic candidate for treating candidiasis.","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1000,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Materials Chemistry B","FirstCategoryId":"1","ListUrlMain":"https://doi.org/10.1039/d4tb00851k","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
Abstract
The scarcity of the antifungal drug arsenal highlights an urgent need to develop alternative treatments for candidiasis caused by Candida albicans (C. albicans). As pH is closely associated with C. albicans infection, it could be an essential target in a novel approach for designing antifungal therapy. In this study, a novel intelligent antifungal monomer, dodecylmethylaminoethyl methacrylate (DMAEM), with a pH-responsive tertiary amine group and a methacrylate-derived CC double bond group is developed. It is uncovered that the two functional groups of DMAEM contribute to a dual mode of action. Under acidic pH, the tertiary amine of DMAEM protonates into a cationic fungicide, sharing similar structural and functional characteristics with quaternary ammonium salts, which exerts fungicidal activity by targeting the CHK1 two-component system in C. albicans. At neutral pH, the methacrylate-derived CC double bond group contributes to anti-virulence activity by blocking hyphal formation. In addition, it is also identified that DMAEM suppresses filamentation by altering the extracellular vesicles of C. albicans. These findings support that the novel intelligent pH-responsive monomer could be a therapeutic candidate for treating candidiasis.
期刊介绍:
Journal of Materials Chemistry A, B & C cover high quality studies across all fields of materials chemistry. The journals focus on those theoretical or experimental studies that report new understanding, applications, properties and synthesis of materials. Journal of Materials Chemistry A, B & C are separated by the intended application of the material studied. Broadly, applications in energy and sustainability are of interest to Journal of Materials Chemistry A, applications in biology and medicine are of interest to Journal of Materials Chemistry B, and applications in optical, magnetic and electronic devices are of interest to Journal of Materials Chemistry C.Journal of Materials Chemistry B is a Transformative Journal and Plan S compliant. Example topic areas within the scope of Journal of Materials Chemistry B are listed below. This list is neither exhaustive nor exclusive:
Antifouling coatings
Biocompatible materials
Bioelectronics
Bioimaging
Biomimetics
Biomineralisation
Bionics
Biosensors
Diagnostics
Drug delivery
Gene delivery
Immunobiology
Nanomedicine
Regenerative medicine & Tissue engineering
Scaffolds
Soft robotics
Stem cells
Therapeutic devices