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...

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Main Authors: Dengfeng Hu, Lingyun Zou, Weijiang Yu, Fan Jia, Haijie Han, Ke Yao, Qiao Jin, Jian Ji
Format: Article
Language:English
Published: Wiley 2020-06-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202000398
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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.
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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
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