Zhiyuan Hu, Jie Shan, Xu Jin, Weijie Sun, Liang Cheng, Xu-Lin Chen, Xianwen Wang
{"title":"原位抗生素释放针状纳米酶的纳米结构,用于靶向和诱导杯突样变死亡,以消灭耐药细菌。","authors":"Zhiyuan Hu, Jie Shan, Xu Jin, Weijie Sun, Liang Cheng, Xu-Lin Chen, Xianwen Wang","doi":"10.1021/acsnano.4c06565","DOIUrl":null,"url":null,"abstract":"<p><p>A series of progress has been made in the field of antimicrobial use of nanozymes due to their superior stability and decreased susceptibility to drug resistance. However, catalytically generated reactive oxygen species (ROS) are insufficient for coping with multidrug-resistant organisms (MDROs) in complex wound environments due to their low targeting ability and insufficient catalytic activity. To address this problem, chemically stable copper-gallic acid-vancomycin (CuGA-VAN) nanoneedles were successfully constructed by a simple approach for targeting bacteria; these nanoneedles exhibit OXD-like and GSH-px-like dual enzyme activities to produce ROS and induce bacterial cuproptosis-like death, thereby eliminating MDRO infections. The results of <i>in vitro</i> experiments showed that the free carboxylic acid of GA could react with the free ammonia of teichoic acid in the <i>methicillin-resistant</i> <i>Staphylococcus aureus</i> (<i>MRSA</i>) cell wall skeleton. Thus, CuGA-VAN nanoneedles can rapidly \"capture\" <i>MRSA</i> in liquid environments, releasing ROS, VAN and Cu<sup>2+</sup> on bacterial surfaces to break down the <i>MRSA</i> barrier, destroying the biofilm. In addition, CuGA-VAN effectively promoted wound repair cell proliferation and angiogenesis to facilitate wound healing while ensuring biosafety. According to transcriptome sequencing, highly internalized Cu<sup>2+</sup> causes copper overload toxicity; downregulates genes related to the bacterial glyoxylate cycle, tricarboxylic acid cycle, and oxidative respiratory chain; and induces lipid peroxidation in the cytoplasm, leading to bacterial cuproptosis-like death. In this study, CuGA-VAN was cleverly designed to trigger a cascade reaction of targeting, drug release, ROS-catalyzed antibacterial activity and cuproptosis-like death. This provides an innovative idea for multidrug-resistant infections.</p>","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":null,"pages":null},"PeriodicalIF":15.8000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Nanoarchitectonics of <i>in Situ</i> Antibiotic-Releasing Acicular Nanozymes for Targeting and Inducing Cuproptosis-like Death to Eliminate Drug-Resistant Bacteria.\",\"authors\":\"Zhiyuan Hu, Jie Shan, Xu Jin, Weijie Sun, Liang Cheng, Xu-Lin Chen, Xianwen Wang\",\"doi\":\"10.1021/acsnano.4c06565\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>A series of progress has been made in the field of antimicrobial use of nanozymes due to their superior stability and decreased susceptibility to drug resistance. However, catalytically generated reactive oxygen species (ROS) are insufficient for coping with multidrug-resistant organisms (MDROs) in complex wound environments due to their low targeting ability and insufficient catalytic activity. To address this problem, chemically stable copper-gallic acid-vancomycin (CuGA-VAN) nanoneedles were successfully constructed by a simple approach for targeting bacteria; these nanoneedles exhibit OXD-like and GSH-px-like dual enzyme activities to produce ROS and induce bacterial cuproptosis-like death, thereby eliminating MDRO infections. The results of <i>in vitro</i> experiments showed that the free carboxylic acid of GA could react with the free ammonia of teichoic acid in the <i>methicillin-resistant</i> <i>Staphylococcus aureus</i> (<i>MRSA</i>) cell wall skeleton. Thus, CuGA-VAN nanoneedles can rapidly \\\"capture\\\" <i>MRSA</i> in liquid environments, releasing ROS, VAN and Cu<sup>2+</sup> on bacterial surfaces to break down the <i>MRSA</i> barrier, destroying the biofilm. In addition, CuGA-VAN effectively promoted wound repair cell proliferation and angiogenesis to facilitate wound healing while ensuring biosafety. According to transcriptome sequencing, highly internalized Cu<sup>2+</sup> causes copper overload toxicity; downregulates genes related to the bacterial glyoxylate cycle, tricarboxylic acid cycle, and oxidative respiratory chain; and induces lipid peroxidation in the cytoplasm, leading to bacterial cuproptosis-like death. In this study, CuGA-VAN was cleverly designed to trigger a cascade reaction of targeting, drug release, ROS-catalyzed antibacterial activity and cuproptosis-like death. 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Nanoarchitectonics of in Situ Antibiotic-Releasing Acicular Nanozymes for Targeting and Inducing Cuproptosis-like Death to Eliminate Drug-Resistant Bacteria.
A series of progress has been made in the field of antimicrobial use of nanozymes due to their superior stability and decreased susceptibility to drug resistance. However, catalytically generated reactive oxygen species (ROS) are insufficient for coping with multidrug-resistant organisms (MDROs) in complex wound environments due to their low targeting ability and insufficient catalytic activity. To address this problem, chemically stable copper-gallic acid-vancomycin (CuGA-VAN) nanoneedles were successfully constructed by a simple approach for targeting bacteria; these nanoneedles exhibit OXD-like and GSH-px-like dual enzyme activities to produce ROS and induce bacterial cuproptosis-like death, thereby eliminating MDRO infections. The results of in vitro experiments showed that the free carboxylic acid of GA could react with the free ammonia of teichoic acid in the methicillin-resistantStaphylococcus aureus (MRSA) cell wall skeleton. Thus, CuGA-VAN nanoneedles can rapidly "capture" MRSA in liquid environments, releasing ROS, VAN and Cu2+ on bacterial surfaces to break down the MRSA barrier, destroying the biofilm. In addition, CuGA-VAN effectively promoted wound repair cell proliferation and angiogenesis to facilitate wound healing while ensuring biosafety. According to transcriptome sequencing, highly internalized Cu2+ causes copper overload toxicity; downregulates genes related to the bacterial glyoxylate cycle, tricarboxylic acid cycle, and oxidative respiratory chain; and induces lipid peroxidation in the cytoplasm, leading to bacterial cuproptosis-like death. In this study, CuGA-VAN was cleverly designed to trigger a cascade reaction of targeting, drug release, ROS-catalyzed antibacterial activity and cuproptosis-like death. This provides an innovative idea for multidrug-resistant infections.
期刊介绍:
ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.