Optimization of Antibacterial Activity and Biosafety through Ultrashort Peptide/Cyclodextrin Inclusion Complexes
Engineered ultrashort peptides, serving as an alternative to natural antimicrobial peptides, offer benefits of simple and modifiable structures, as well as ease of assembly. Achieving excellent antibacterial performance and favorable biocompatibility through structural optimization remains essential...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/19/14801 |
| _version_ | 1797447250968838144 |
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| author | Hang Liu Lin Wang Chen Yao |
| author_facet | Hang Liu Lin Wang Chen Yao |
| author_sort | Hang Liu |
| collection | DOAJ |
| description | Engineered ultrashort peptides, serving as an alternative to natural antimicrobial peptides, offer benefits of simple and modifiable structures, as well as ease of assembly. Achieving excellent antibacterial performance and favorable biocompatibility through structural optimization remains essential for further applications. In this study, we assembled lipoic acid (LA)–modified tripeptide RWR (LA–RWR) with β–cyclodextrin (β–CD) to form nano–inclusion complexes. The free cationic tripeptide region in the nano–inclusion complex provided high antibacterial activity, while β–CD enhanced its biocompatibility. Compared with peptides (LA–RWR, LA–RWR–phenethylamine) alone, inclusion complexes exhibited lower minimum inhibitory concentrations/minimum bactericidal concentrations (MICs/MBCs) against typical Gram–negative/Gram–positive bacteria and fungi, along with improved planktonic killing kinetics and antibiofilm efficiency. The antibacterial mechanism of the nano–inclusion complexes was confirmed through depolarization experiments, outer membrane permeability experiments, and confocal laser scanning microscopy observations. Furthermore, biological evaluations indicated that the hemolysis rate of the inclusion complexes decreased to half or even lower at high concentrations, and cell viability was superior to that of the non–included peptides. Preliminary in vivo studies suggested that the inclusion complexes, optimized for antibacterial activity and biosafety, could be used as promising antibacterial agents for potential applications. |
| first_indexed | 2024-03-09T13:52:11Z |
| format | Article |
| id | doaj.art-8827a6c3f30044e5b29bf7c7c6c56764 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:52:11Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8827a6c3f30044e5b29bf7c7c6c567642023-11-30T20:48:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124191480110.3390/ijms241914801Optimization of Antibacterial Activity and Biosafety through Ultrashort Peptide/Cyclodextrin Inclusion ComplexesHang Liu0Lin Wang1Chen Yao2School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, ChinaSchool of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, ChinaSchool of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, ChinaEngineered ultrashort peptides, serving as an alternative to natural antimicrobial peptides, offer benefits of simple and modifiable structures, as well as ease of assembly. Achieving excellent antibacterial performance and favorable biocompatibility through structural optimization remains essential for further applications. In this study, we assembled lipoic acid (LA)–modified tripeptide RWR (LA–RWR) with β–cyclodextrin (β–CD) to form nano–inclusion complexes. The free cationic tripeptide region in the nano–inclusion complex provided high antibacterial activity, while β–CD enhanced its biocompatibility. Compared with peptides (LA–RWR, LA–RWR–phenethylamine) alone, inclusion complexes exhibited lower minimum inhibitory concentrations/minimum bactericidal concentrations (MICs/MBCs) against typical Gram–negative/Gram–positive bacteria and fungi, along with improved planktonic killing kinetics and antibiofilm efficiency. The antibacterial mechanism of the nano–inclusion complexes was confirmed through depolarization experiments, outer membrane permeability experiments, and confocal laser scanning microscopy observations. Furthermore, biological evaluations indicated that the hemolysis rate of the inclusion complexes decreased to half or even lower at high concentrations, and cell viability was superior to that of the non–included peptides. Preliminary in vivo studies suggested that the inclusion complexes, optimized for antibacterial activity and biosafety, could be used as promising antibacterial agents for potential applications.https://www.mdpi.com/1422-0067/24/19/14801antimicrobial peptideβ–cyclodextrininclusion complexesantibacterial activitybiosafety |
| spellingShingle | Hang Liu Lin Wang Chen Yao Optimization of Antibacterial Activity and Biosafety through Ultrashort Peptide/Cyclodextrin Inclusion Complexes International Journal of Molecular Sciences antimicrobial peptide β–cyclodextrin inclusion complexes antibacterial activity biosafety |
| title | Optimization of Antibacterial Activity and Biosafety through Ultrashort Peptide/Cyclodextrin Inclusion Complexes |
| title_full | Optimization of Antibacterial Activity and Biosafety through Ultrashort Peptide/Cyclodextrin Inclusion Complexes |
| title_fullStr | Optimization of Antibacterial Activity and Biosafety through Ultrashort Peptide/Cyclodextrin Inclusion Complexes |
| title_full_unstemmed | Optimization of Antibacterial Activity and Biosafety through Ultrashort Peptide/Cyclodextrin Inclusion Complexes |
| title_short | Optimization of Antibacterial Activity and Biosafety through Ultrashort Peptide/Cyclodextrin Inclusion Complexes |
| title_sort | optimization of antibacterial activity and biosafety through ultrashort peptide cyclodextrin inclusion complexes |
| topic | antimicrobial peptide β–cyclodextrin inclusion complexes antibacterial activity biosafety |
| url | https://www.mdpi.com/1422-0067/24/19/14801 |
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