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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| Format: | Article |
| Language: | English |
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BMC
2025-08-01
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| Series: | Journal of Nanobiotechnology |
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| 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 |
| id | doaj-art-e60c7df98fcf4bc29050968659a71c62 |
| 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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