Self-assembled nanopeptide dendrites with high antifungal activity and protease hydrolytic stability for fungal keratitis treatment

Abstract The excessive use of antibiotics in recent years has contributed to an increase in microbial resistance, thereby compromising the health of both humans and animals and necessitating the development of innovative therapeutic strategies. In this study, we have creatively integrated fatty acid...

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Main Authors: Guoyu Li, Hongyu Chen, Wenwen Chen, Zhenheng Lai, Yinfeng Lyu, Anshan Shan
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-025-03670-x
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author Guoyu Li
Hongyu Chen
Wenwen Chen
Zhenheng Lai
Yinfeng Lyu
Anshan Shan
author_facet Guoyu Li
Hongyu Chen
Wenwen Chen
Zhenheng Lai
Yinfeng Lyu
Anshan Shan
author_sort Guoyu Li
collection DOAJ
description Abstract The excessive use of antibiotics in recent years has contributed to an increase in microbial resistance, thereby compromising the health of both humans and animals and necessitating the development of innovative therapeutic strategies. In this study, we have creatively integrated fatty acids into the previously reported anti-enzymolysis unit (CRKP) in a branched configuration, resulting in the design and fabrication of a series of peptide dendritic with potent antifungal and anti-drug-resistant fungal activities. Notably, peptide dendron C8-2 exhibited significantly enhanced antifungal efficacy, favorable in vitro biocompatibility, and remarkable stability in the presence of serum and proteases. Mechanistic investigations reveal that C8-2 exert their antifungal effects by increasing cell wall permeability, inducing plasma membrane depolarization, leading to membrane rupture and content release, and generating reactive oxygen species. In addition, peptide dendron C8-2 can effectively eliminate Candida albicans from the eyeball in fungal-induced keratitis in mice, and the treatment effect is significantly superior to that of amphotericin B. Consequently, the self-assembled peptide dendron nanoparticles of C8-2 hold significant potential as antifungal agents. Additionally, their robust antifungal activity and stability against resistance may effectively address the growing challenge of drug-resistant fungal strains, thereby facilitating the development of future peptide nanoparticle-based therapies. Graphical abstract
format Article
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institution Kabale University
issn 1477-3155
language English
publishDate 2025-08-01
publisher BMC
record_format Article
series Journal of Nanobiotechnology
spelling doaj-art-e60c7df98fcf4bc29050968659a71c622025-08-24T11:48:49ZengBMCJournal of Nanobiotechnology1477-31552025-08-0123111610.1186/s12951-025-03670-xSelf-assembled nanopeptide dendrites with high antifungal activity and protease hydrolytic stability for fungal keratitis treatmentGuoyu Li0Hongyu Chen1Wenwen Chen2Zhenheng Lai3Yinfeng Lyu4Anshan Shan5College of Animal Science and Technology, Northeast Agricultural UniversityCollege of Animal Science and Technology, Northeast Agricultural UniversityCollege of Animal Science and Technology, Northeast Agricultural UniversityCollege of Animal Science and Technology, Northeast Agricultural UniversityCollege of Animal Science and Technology, Northeast Agricultural UniversityCollege of Animal Science and Technology, Northeast Agricultural UniversityAbstract The excessive use of antibiotics in recent years has contributed to an increase in microbial resistance, thereby compromising the health of both humans and animals and necessitating the development of innovative therapeutic strategies. In this study, we have creatively integrated fatty acids into the previously reported anti-enzymolysis unit (CRKP) in a branched configuration, resulting in the design and fabrication of a series of peptide dendritic with potent antifungal and anti-drug-resistant fungal activities. Notably, peptide dendron C8-2 exhibited significantly enhanced antifungal efficacy, favorable in vitro biocompatibility, and remarkable stability in the presence of serum and proteases. Mechanistic investigations reveal that C8-2 exert their antifungal effects by increasing cell wall permeability, inducing plasma membrane depolarization, leading to membrane rupture and content release, and generating reactive oxygen species. In addition, peptide dendron C8-2 can effectively eliminate Candida albicans from the eyeball in fungal-induced keratitis in mice, and the treatment effect is significantly superior to that of amphotericin B. Consequently, the self-assembled peptide dendron nanoparticles of C8-2 hold significant potential as antifungal agents. Additionally, their robust antifungal activity and stability against resistance may effectively address the growing challenge of drug-resistant fungal strains, thereby facilitating the development of future peptide nanoparticle-based therapies. Graphical abstracthttps://doi.org/10.1186/s12951-025-03670-xSelf-assembling nanoparticlesAntifungal activityStabilityMechanism of actionIn vivo efficacy
spellingShingle Guoyu Li
Hongyu Chen
Wenwen Chen
Zhenheng Lai
Yinfeng Lyu
Anshan Shan
Self-assembled nanopeptide dendrites with high antifungal activity and protease hydrolytic stability for fungal keratitis treatment
Journal of Nanobiotechnology
Self-assembling nanoparticles
Antifungal activity
Stability
Mechanism of action
In vivo efficacy
title Self-assembled nanopeptide dendrites with high antifungal activity and protease hydrolytic stability for fungal keratitis treatment
title_full Self-assembled nanopeptide dendrites with high antifungal activity and protease hydrolytic stability for fungal keratitis treatment
title_fullStr Self-assembled nanopeptide dendrites with high antifungal activity and protease hydrolytic stability for fungal keratitis treatment
title_full_unstemmed Self-assembled nanopeptide dendrites with high antifungal activity and protease hydrolytic stability for fungal keratitis treatment
title_short Self-assembled nanopeptide dendrites with high antifungal activity and protease hydrolytic stability for fungal keratitis treatment
title_sort self assembled nanopeptide dendrites with high antifungal activity and protease hydrolytic stability for fungal keratitis treatment
topic Self-assembling nanoparticles
Antifungal activity
Stability
Mechanism of action
In vivo efficacy
url https://doi.org/10.1186/s12951-025-03670-x
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