Relief of Biofilm Hypoxia Using an Oxygen Nanocarrier: A New Paradigm for Enhanced Antibiotic Therapy
Abstract Biofilms are chief culprits of most intractable infections and pose great threats to human health. Conventional antibiotic therapies are hypodynamic to biofilms due to their strong drug resistance, closely related with biofilm hypoxia. A new strategy for enhanced antibiotic therapy by relie...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2020-06-01
|
Series: | Advanced Science |
Subjects: | |
Online Access: | https://doi.org/10.1002/advs.202000398 |
_version_ | 1819198828381732864 |
---|---|
author | Dengfeng Hu Lingyun Zou Weijiang Yu Fan Jia Haijie Han Ke Yao Qiao Jin Jian Ji |
author_facet | Dengfeng Hu Lingyun Zou Weijiang Yu Fan Jia Haijie Han Ke Yao Qiao Jin Jian Ji |
author_sort | Dengfeng Hu |
collection | DOAJ |
description | Abstract Biofilms are chief culprits of most intractable infections and pose great threats to human health. Conventional antibiotic therapies are hypodynamic to biofilms due to their strong drug resistance, closely related with biofilm hypoxia. A new strategy for enhanced antibiotic therapy by relieving biofilm hypoxia is reported here. A two‐step sequential delivery strategy is fabricated using perfluorohexane (PFH)‐loaded liposomes (lip) as oxygen (O2) carriers (denoted as lip@PFH@O2) and commercial antibiotics. The results indicate that the two‐step sequential treatment exhibits much lower minimum bactericidal concentrations than the antibiotic treatment alone. In this design, the lip@PFH@O2 holds positively charged surface for better biofilm penetration. After penetrating into biofilm, oxygen can be released from lip@PFH@O2 by inches, which greatly relieves biofilm hypoxia. With the relief of hypoxia, the quorum sensing and the drug efflux pumps of bacteria are suppressed by restraining related gene expression, leading to the reduced antibiotic resistance. Furthermore, the in vivo experimental results also demonstrate that lip@PFH@O2 can effectively relieve biofilm hypoxia and enhance therapeutic efficacy of antibiotics. As a proof‐of‐concept, this research provides an innovative strategy for enhanced antibiotic therapy by relieving hypoxia, which may hold a bright future in combating biofilm‐associated infections. |
first_indexed | 2024-12-23T03:06:39Z |
format | Article |
id | doaj.art-d85c2bb5cc82450cb30c6d939e132b65 |
institution | Directory Open Access Journal |
issn | 2198-3844 |
language | English |
last_indexed | 2024-12-23T03:06:39Z |
publishDate | 2020-06-01 |
publisher | Wiley |
record_format | Article |
series | Advanced Science |
spelling | doaj.art-d85c2bb5cc82450cb30c6d939e132b652022-12-21T18:02:18ZengWileyAdvanced Science2198-38442020-06-01712n/an/a10.1002/advs.202000398Relief of Biofilm Hypoxia Using an Oxygen Nanocarrier: A New Paradigm for Enhanced Antibiotic TherapyDengfeng Hu0Lingyun Zou1Weijiang Yu2Fan Jia3Haijie Han4Ke Yao5Qiao Jin6Jian Ji7MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering Zhejiang University Hangzhou Zhejiang Province 310027 P. R. ChinaMOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering Zhejiang University Hangzhou Zhejiang Province 310027 P. R. ChinaMOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering Zhejiang University Hangzhou Zhejiang Province 310027 P. R. ChinaMOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering Zhejiang University Hangzhou Zhejiang Province 310027 P. R. ChinaEye Center Second Affiliated Hospital, School of Medicine Zhejiang University Hangzhou Zhejiang Province 310027 P. R. ChinaEye Center Second Affiliated Hospital, School of Medicine Zhejiang University Hangzhou Zhejiang Province 310027 P. R. ChinaMOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering Zhejiang University Hangzhou Zhejiang Province 310027 P. R. ChinaMOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering Zhejiang University Hangzhou Zhejiang Province 310027 P. R. ChinaAbstract Biofilms are chief culprits of most intractable infections and pose great threats to human health. Conventional antibiotic therapies are hypodynamic to biofilms due to their strong drug resistance, closely related with biofilm hypoxia. A new strategy for enhanced antibiotic therapy by relieving biofilm hypoxia is reported here. A two‐step sequential delivery strategy is fabricated using perfluorohexane (PFH)‐loaded liposomes (lip) as oxygen (O2) carriers (denoted as lip@PFH@O2) and commercial antibiotics. The results indicate that the two‐step sequential treatment exhibits much lower minimum bactericidal concentrations than the antibiotic treatment alone. In this design, the lip@PFH@O2 holds positively charged surface for better biofilm penetration. After penetrating into biofilm, oxygen can be released from lip@PFH@O2 by inches, which greatly relieves biofilm hypoxia. With the relief of hypoxia, the quorum sensing and the drug efflux pumps of bacteria are suppressed by restraining related gene expression, leading to the reduced antibiotic resistance. Furthermore, the in vivo experimental results also demonstrate that lip@PFH@O2 can effectively relieve biofilm hypoxia and enhance therapeutic efficacy of antibiotics. As a proof‐of‐concept, this research provides an innovative strategy for enhanced antibiotic therapy by relieving hypoxia, which may hold a bright future in combating biofilm‐associated infections.https://doi.org/10.1002/advs.202000398antibiotic resistanceantibioticsbiofilmshypoxiaperfluorohexane |
spellingShingle | Dengfeng Hu Lingyun Zou Weijiang Yu Fan Jia Haijie Han Ke Yao Qiao Jin Jian Ji Relief of Biofilm Hypoxia Using an Oxygen Nanocarrier: A New Paradigm for Enhanced Antibiotic Therapy Advanced Science antibiotic resistance antibiotics biofilms hypoxia perfluorohexane |
title | Relief of Biofilm Hypoxia Using an Oxygen Nanocarrier: A New Paradigm for Enhanced Antibiotic Therapy |
title_full | Relief of Biofilm Hypoxia Using an Oxygen Nanocarrier: A New Paradigm for Enhanced Antibiotic Therapy |
title_fullStr | Relief of Biofilm Hypoxia Using an Oxygen Nanocarrier: A New Paradigm for Enhanced Antibiotic Therapy |
title_full_unstemmed | Relief of Biofilm Hypoxia Using an Oxygen Nanocarrier: A New Paradigm for Enhanced Antibiotic Therapy |
title_short | Relief of Biofilm Hypoxia Using an Oxygen Nanocarrier: A New Paradigm for Enhanced Antibiotic Therapy |
title_sort | relief of biofilm hypoxia using an oxygen nanocarrier a new paradigm for enhanced antibiotic therapy |
topic | antibiotic resistance antibiotics biofilms hypoxia perfluorohexane |
url | https://doi.org/10.1002/advs.202000398 |
work_keys_str_mv | AT dengfenghu reliefofbiofilmhypoxiausinganoxygennanocarrieranewparadigmforenhancedantibiotictherapy AT lingyunzou reliefofbiofilmhypoxiausinganoxygennanocarrieranewparadigmforenhancedantibiotictherapy AT weijiangyu reliefofbiofilmhypoxiausinganoxygennanocarrieranewparadigmforenhancedantibiotictherapy AT fanjia reliefofbiofilmhypoxiausinganoxygennanocarrieranewparadigmforenhancedantibiotictherapy AT haijiehan reliefofbiofilmhypoxiausinganoxygennanocarrieranewparadigmforenhancedantibiotictherapy AT keyao reliefofbiofilmhypoxiausinganoxygennanocarrieranewparadigmforenhancedantibiotictherapy AT qiaojin reliefofbiofilmhypoxiausinganoxygennanocarrieranewparadigmforenhancedantibiotictherapy AT jianji reliefofbiofilmhypoxiausinganoxygennanocarrieranewparadigmforenhancedantibiotictherapy |