Responsive Assembly of Silver Nanoclusters with a Biofilm Locally Amplified Bactericidal Effect to Enhance Treatments against Multi-Drug-Resistant Bacterial Infections.
Identifieur interne : 000237 ( Main/Corpus ); précédent : 000236; suivant : 000238Responsive Assembly of Silver Nanoclusters with a Biofilm Locally Amplified Bactericidal Effect to Enhance Treatments against Multi-Drug-Resistant Bacterial Infections.
Auteurs : Jiahe Wu ; Fangyuan Li ; Xi Hu ; Jingxiong Lu ; Xiaolian Sun ; Jianqing Gao ; Daishun LingSource :
- ACS central science [ 2374-7943 ] ; 2019.
Abstract
Bacterial biofilms pose a major threat to public health because they are resistant to most current therapeutics. Conventional antibiotics exhibit limited penetration and weakened activity in the acidic microenvironment of a biofilm. Here, the development of biofilm-responsive nanoantibiotics (rAgNAs) composed of self-assembled silver nanoclusters and pH-sensitive charge reversal ligands, whose bactericidal activity can be selectively boosted in the biofilm microenvironment, is reported. Under neutral physiological conditions, the bactericidal activity of rAgNAs is self-quenched because the toxic silver ions' release is largely inhibited; however, upon entry into the acidic biofilm microenvironment, the rAgNAs not only exhibit charge reversal to facilitate local accumulation and retention but also disassemble into small silver nanoclusters, thus enabling deep penetration and accelerated silver ions release for dramatically amplified bactericidal activity. The superior antibiofilm activity of rAgNAs is demonstrated both in vitro and in vivo, and the mortality rate of mice with multi-drug-resistant biofilm-induced severe pyomyositis can be significantly reduced by rAgNAs treatment, indicating the immense potential of rAgNAs as highly efficient nanoscale antibacterial agents to combat resistant bacterial biofilm-associated infections.
DOI: 10.1021/acscentsci.9b00359
PubMed: 31482119
PubMed Central: PMC6716126
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R. China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Fangyuan" sort="Li, Fangyuan" uniqKey="Li F" first="Fangyuan" last="Li">Fangyuan Li</name><affiliation><nlm:affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Hu, Xi" sort="Hu, Xi" uniqKey="Hu X" first="Xi" last="Hu">Xi Hu</name><affiliation><nlm:affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Lu, Jingxiong" sort="Lu, Jingxiong" uniqKey="Lu J" first="Jingxiong" last="Lu">Jingxiong Lu</name><affiliation><nlm:affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Sun, Xiaolian" sort="Sun, Xiaolian" uniqKey="Sun X" first="Xiaolian" last="Sun">Xiaolian Sun</name><affiliation><nlm:affiliation>Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, P. R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Gao, Jianqing" sort="Gao, Jianqing" uniqKey="Gao J" first="Jianqing" last="Gao">Jianqing Gao</name><affiliation><nlm:affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</nlm:affiliation></affiliation></author><author><name sortKey="Ling, Daishun" sort="Ling, Daishun" uniqKey="Ling D" first="Daishun" last="Ling">Daishun Ling</name><affiliation><nlm:affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</nlm:affiliation></affiliation></author></analytic><series><title level="j">ACS central science</title><idno type="ISSN">2374-7943</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Bacterial biofilms pose a major threat to public health because they are resistant to most current therapeutics. Conventional antibiotics exhibit limited penetration and weakened activity in the acidic microenvironment of a biofilm. Here, the development of biofilm-responsive nanoantibiotics (rAgNAs) composed of self-assembled silver nanoclusters and pH-sensitive charge reversal ligands, whose bactericidal activity can be selectively boosted in the biofilm microenvironment, is reported. Under neutral physiological conditions, the bactericidal activity of rAgNAs is self-quenched because the toxic silver ions' release is largely inhibited; however, upon entry into the acidic biofilm microenvironment, the rAgNAs not only exhibit charge reversal to facilitate local accumulation and retention but also disassemble into small silver nanoclusters, thus enabling deep penetration and accelerated silver ions release for dramatically amplified bactericidal activity. The superior antibiofilm activity of rAgNAs is demonstrated both in vitro and in vivo, and the mortality rate of mice with multi-drug-resistant biofilm-induced severe pyomyositis can be significantly reduced by rAgNAs treatment, indicating the immense potential of rAgNAs as highly efficient nanoscale antibacterial agents to combat resistant bacterial biofilm-associated infections.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">31482119</PMID><DateRevised><Year>2020</Year><Month>10</Month><Day>01</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">2374-7943</ISSN><JournalIssue CitedMedium="Print"><Volume>5</Volume><Issue>8</Issue><PubDate><Year>2019</Year><Month>Aug</Month><Day>28</Day></PubDate></JournalIssue><Title>ACS central science</Title><ISOAbbreviation>ACS Cent Sci</ISOAbbreviation></Journal><ArticleTitle>Responsive Assembly of Silver Nanoclusters with a Biofilm Locally Amplified Bactericidal Effect to Enhance Treatments against Multi-Drug-Resistant Bacterial Infections.</ArticleTitle><Pagination><MedlinePgn>1366-1376</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1021/acscentsci.9b00359</ELocationID><Abstract><AbstractText>Bacterial biofilms pose a major threat to public health because they are resistant to most current therapeutics. Conventional antibiotics exhibit limited penetration and weakened activity in the acidic microenvironment of a biofilm. Here, the development of biofilm-responsive nanoantibiotics (rAgNAs) composed of self-assembled silver nanoclusters and pH-sensitive charge reversal ligands, whose bactericidal activity can be selectively boosted in the biofilm microenvironment, is reported. Under neutral physiological conditions, the bactericidal activity of rAgNAs is self-quenched because the toxic silver ions' release is largely inhibited; however, upon entry into the acidic biofilm microenvironment, the rAgNAs not only exhibit charge reversal to facilitate local accumulation and retention but also disassemble into small silver nanoclusters, thus enabling deep penetration and accelerated silver ions release for dramatically amplified bactericidal activity. The superior antibiofilm activity of rAgNAs is demonstrated both in vitro and in vivo, and the mortality rate of mice with multi-drug-resistant biofilm-induced severe pyomyositis can be significantly reduced by rAgNAs treatment, indicating the immense potential of rAgNAs as highly efficient nanoscale antibacterial agents to combat resistant bacterial biofilm-associated infections.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Jiahe</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Fangyuan</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hu</LastName><ForeName>Xi</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lu</LastName><ForeName>Jingxiong</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sun</LastName><ForeName>Xiaolian</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, P. R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gao</LastName><ForeName>Jianqing</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ling</LastName><ForeName>Daishun</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Pharmaceutics, College of Pharmaceutical Sciences, Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, and Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, P. R. China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>06</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>ACS Cent Sci</MedlineTA><NlmUniqueID>101660035</NlmUniqueID><ISSNLinking>2374-7943</ISSNLinking></MedlineJournalInfo><CoiStatement>The authors declare no competing financial interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>04</Month><Day>08</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>9</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>9</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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