Enhanced penetration and biofilm eradication by sophorolipid micelles encapsulating Honokiol: a comprehensive solution for biofilm-associated lung infections

Abstract Background Biofilm-associated lung infections, particularly those caused by Staphylococcus aureus (S. aureus), pose significant clinical challenges to conventional therapies. S. aureus Biofilm infections are refractory to treatment due to the presence of persister bacterial cells and the ba...

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Main Authors: Shiyu Lin, Xiaojuan Li, Wei Zhang, Gang Shu, Tim Tolker-Nielsen, Haohuan Li, Funeng Xu, Juchun Lin, Guangneng Peng, Li Zhang, Hualin Fu
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Journal of Nanobiotechnology
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Online Access:https://doi.org/10.1186/s12951-025-03144-0
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author Shiyu Lin
Xiaojuan Li
Wei Zhang
Gang Shu
Tim Tolker-Nielsen
Haohuan Li
Funeng Xu
Juchun Lin
Guangneng Peng
Li Zhang
Hualin Fu
author_facet Shiyu Lin
Xiaojuan Li
Wei Zhang
Gang Shu
Tim Tolker-Nielsen
Haohuan Li
Funeng Xu
Juchun Lin
Guangneng Peng
Li Zhang
Hualin Fu
author_sort Shiyu Lin
collection DOAJ
description Abstract Background Biofilm-associated lung infections, particularly those caused by Staphylococcus aureus (S. aureus), pose significant clinical challenges to conventional therapies. S. aureus Biofilm infections are refractory to treatment due to the presence of persister bacterial cells and the barrier effect of unique extracellular polymeric substances (EPS). Results This study describes the development of multifunctional micelles, HK-SL Ms, utilizing sophorolipid (SL) to encapsulate Honokiol (HK). HK-SL Ms potently disrupted the EPS barrier, killed some internal colonizing bacteria, and inhibited further bacterial adhesion. Consequently, the dynamic cycling of biofilms was hindered, achieving a promising removal of S. aureus biofilms. In vitro studies demonstrated that HK-SL Ms exhibited significant antimicrobial reduction of a 6.42 log10CFU/mL. HK-SL Ms eradicated 71.73% of biofilms by targeting extracellular polysaccharides, extracellular proteins, and viable cells within the biofilm. Additionally, 1.66 log10CFU/mL units of S. aureus within biofilms were killed. Moreover, HK-SL Ms inhibited 91.10% of early S. aureus biofilm formation by obstructing initial bacterial adhesion and the formation of extracellular polysaccharides and polysaccharide intercellular adhesins (PIA). Thus, the reestablishment and reinfection of S. aureus biofilms could be resolved promisingly. Biofilm infections are as predominant in acute pneumonia as in chronic cases, inducing similar lung inflammation. In a murine model of pneumonia infected by S. aureus, HK-SL Ms significantly reduced the bacterial load in the lungs, decreased inflammatory factor levels, and repaired lung tissue damage. Conclusions HK-SL Ms offers a novel strategy for the clinical treatment of biofilm-associated infections by dispersing and removing S. aureus biofilms and preventing new infections. Graphical Abstract
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institution Kabale University
issn 1477-3155
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publishDate 2025-02-01
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spelling doaj-art-8f9ce4f0d07b4c129c2abbe2137b43da2025-02-09T12:53:02ZengBMCJournal of Nanobiotechnology1477-31552025-02-0123111610.1186/s12951-025-03144-0Enhanced penetration and biofilm eradication by sophorolipid micelles encapsulating Honokiol: a comprehensive solution for biofilm-associated lung infectionsShiyu Lin0Xiaojuan Li1Wei Zhang2Gang Shu3Tim Tolker-Nielsen4Haohuan Li5Funeng Xu6Juchun Lin7Guangneng Peng8Li Zhang9Hualin Fu10Innovative Engineering Research Center of Veterinary Pharmaceutics,, Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural UniversityInnovative Engineering Research Center of Veterinary Pharmaceutics,, Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural UniversityInnovative Engineering Research Center of Veterinary Pharmaceutics,, Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural UniversityInnovative Engineering Research Center of Veterinary Pharmaceutics,, Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural UniversityDepartment of Immunology and Microbiology, Costerton Biofilm Center, University of CopenhagenInnovative Engineering Research Center of Veterinary Pharmaceutics,, Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural UniversityInnovative Engineering Research Center of Veterinary Pharmaceutics,, Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural UniversityInnovative Engineering Research Center of Veterinary Pharmaceutics,, Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural UniversityInnovative Engineering Research Center of Veterinary Pharmaceutics,, Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural UniversitySichuan Academy of Chinese Medicine SciencesInnovative Engineering Research Center of Veterinary Pharmaceutics,, Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural UniversityAbstract Background Biofilm-associated lung infections, particularly those caused by Staphylococcus aureus (S. aureus), pose significant clinical challenges to conventional therapies. S. aureus Biofilm infections are refractory to treatment due to the presence of persister bacterial cells and the barrier effect of unique extracellular polymeric substances (EPS). Results This study describes the development of multifunctional micelles, HK-SL Ms, utilizing sophorolipid (SL) to encapsulate Honokiol (HK). HK-SL Ms potently disrupted the EPS barrier, killed some internal colonizing bacteria, and inhibited further bacterial adhesion. Consequently, the dynamic cycling of biofilms was hindered, achieving a promising removal of S. aureus biofilms. In vitro studies demonstrated that HK-SL Ms exhibited significant antimicrobial reduction of a 6.42 log10CFU/mL. HK-SL Ms eradicated 71.73% of biofilms by targeting extracellular polysaccharides, extracellular proteins, and viable cells within the biofilm. Additionally, 1.66 log10CFU/mL units of S. aureus within biofilms were killed. Moreover, HK-SL Ms inhibited 91.10% of early S. aureus biofilm formation by obstructing initial bacterial adhesion and the formation of extracellular polysaccharides and polysaccharide intercellular adhesins (PIA). Thus, the reestablishment and reinfection of S. aureus biofilms could be resolved promisingly. Biofilm infections are as predominant in acute pneumonia as in chronic cases, inducing similar lung inflammation. In a murine model of pneumonia infected by S. aureus, HK-SL Ms significantly reduced the bacterial load in the lungs, decreased inflammatory factor levels, and repaired lung tissue damage. Conclusions HK-SL Ms offers a novel strategy for the clinical treatment of biofilm-associated infections by dispersing and removing S. aureus biofilms and preventing new infections. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03144-0Staphylococcus aureus biofilmSophorolipidHonokiolNanomicelle
spellingShingle Shiyu Lin
Xiaojuan Li
Wei Zhang
Gang Shu
Tim Tolker-Nielsen
Haohuan Li
Funeng Xu
Juchun Lin
Guangneng Peng
Li Zhang
Hualin Fu
Enhanced penetration and biofilm eradication by sophorolipid micelles encapsulating Honokiol: a comprehensive solution for biofilm-associated lung infections
Journal of Nanobiotechnology
Staphylococcus aureus biofilm
Sophorolipid
Honokiol
Nanomicelle
title Enhanced penetration and biofilm eradication by sophorolipid micelles encapsulating Honokiol: a comprehensive solution for biofilm-associated lung infections
title_full Enhanced penetration and biofilm eradication by sophorolipid micelles encapsulating Honokiol: a comprehensive solution for biofilm-associated lung infections
title_fullStr Enhanced penetration and biofilm eradication by sophorolipid micelles encapsulating Honokiol: a comprehensive solution for biofilm-associated lung infections
title_full_unstemmed Enhanced penetration and biofilm eradication by sophorolipid micelles encapsulating Honokiol: a comprehensive solution for biofilm-associated lung infections
title_short Enhanced penetration and biofilm eradication by sophorolipid micelles encapsulating Honokiol: a comprehensive solution for biofilm-associated lung infections
title_sort enhanced penetration and biofilm eradication by sophorolipid micelles encapsulating honokiol a comprehensive solution for biofilm associated lung infections
topic Staphylococcus aureus biofilm
Sophorolipid
Honokiol
Nanomicelle
url https://doi.org/10.1186/s12951-025-03144-0
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