Journal
ACS NANO
Volume 17, Issue 20, Pages 19685-19695Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.3c02886
Keywords
antibacterial gold nanoclusters; nanoantibiotics; vancomycin-resistant bacteria; ototoxicity; multiple administration modes
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This study focuses on the issues of drug resistance and high toxicity in vancomycin, and presents mercaptophenylboronic acid (MBA)-modified gold nanoclusters (Au-44(MBA)(18)) as a solution. The results show that Au-44(MBA)(18) exhibits excellent antibacterial activities against drug-resistant bacteria and can interact with bacteria by attaching to teichoic-acid and destroying the cell wall, as well as binding to bacterial DNA. It has multiple administration routes and high biosafety, making it a potential nanoantibiotic for treating multidrug-resistant bacterial infections.
Vancomycin is one of the last lines of defense against certain drug-resistant bacteria-caused infections. However, the high susceptibility to drug resistance and high toxicity seriously limit the application of vancomycin. Nanoantibiotics provide opportunities to solve these problems. Herein, we present mercaptophenylboronic acid (MBA)-modified gold nanoclusters with well-defined molecular formulas and structure (Au-44(MBA)(18)) and excellent antibacterial activities against various drug-resistant bacteria such as vancomycin-resistant Enterococcus faecalis (VRE). Au-44(MBA)(18) interacts with bacteria by first attaching to teichoic-acid and destroying the cell wall and subsequently binding to the bacterial DNA. Au-44(MBA)(18) could be administered via multiple routes and has a high biosafety (500 mg/kg, no ototoxicity), overcoming the two major shortcomings of vancomycin (sole administration route and high ototoxicity). Our study is insightful for curing infections caused by multidrug-resistant bacteria using nanoantibiotics with high biosafety.
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