Amphiphilic mPEG-PLGA copolymer nanoparticles co-delivering colistin and niclosamide to treat colistin-resistant Gram-negative bacteria infections
Abstract Colistin is the last line of defense against multidrug-resistant (MDR) Gram-negative bacterial infections, yet it is restricted due to high drug resistance and toxicity. The combination therapy of colistin and niclosamide exhibits excellent synergistic antibacterial activity against Gram-ne...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-04-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08095-8 |
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| author | Kaifang Yi Xilong Wang Pengliang Li Yanling Gao Dandan He Yushan Pan Xiaoyuan Ma Gongzheng Hu Yajun Zhai |
| author_facet | Kaifang Yi Xilong Wang Pengliang Li Yanling Gao Dandan He Yushan Pan Xiaoyuan Ma Gongzheng Hu Yajun Zhai |
| author_sort | Kaifang Yi |
| collection | DOAJ |
| description | Abstract Colistin is the last line of defense against multidrug-resistant (MDR) Gram-negative bacterial infections, yet it is restricted due to high drug resistance and toxicity. The combination therapy of colistin and niclosamide exhibits excellent synergistic antibacterial activity against Gram-negative bacteria. How to co-deliver these two drugs with vastly different pharmacokinetic properties in sufficient amounts to the infection site is the core issue that must be resolved for the clinical translation of this drug combination. Here, we designed and prepared a nanosystem capable of co-loading colistin and niclosamide with different physicochemical properties into mPEG-PLGA nanoparticles (COL/NIC-mPEG-PLGA-NPs) to overcome the resistance of multiple colistin-resistant bacteria to colistin and alleviate its toxicity. Mechanistic studies revealed that the COL/NIC-mPEG-PLGA-NPs enhanced the affinity of delivered COL to the modified membrane of colistin-resistant bacteria. The increased membrane permeability caused by colistin promotes an influx of niclosamide, which reduces efflux pump activity and generates intracellular ROS stress, eliminating colistin-resistant bacteria. In addition, the nanoparticles proved non-toxic both in vitro and in vivo. Overall, our study has profound insights into the use of nanosystems with high biosafety for the treatment of infections caused by colistin-resistant bacteria. |
| format | Article |
| id | doaj-art-f8bac4b85e644b8a8392ffc21b96b24b |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-f8bac4b85e644b8a8392ffc21b96b24b2025-08-20T03:52:23ZengNature PortfolioCommunications Biology2399-36422025-04-018111410.1038/s42003-025-08095-8Amphiphilic mPEG-PLGA copolymer nanoparticles co-delivering colistin and niclosamide to treat colistin-resistant Gram-negative bacteria infectionsKaifang Yi0Xilong Wang1Pengliang Li2Yanling Gao3Dandan He4Yushan Pan5Xiaoyuan Ma6Gongzheng Hu7Yajun Zhai8Henan Agricultural UniversityHenan Agricultural UniversityHenan Agricultural UniversityHenan vocational college of AgricultureHenan Agricultural UniversityHenan Agricultural UniversityHenan Agricultural UniversityHenan Agricultural UniversityHenan Agricultural UniversityAbstract Colistin is the last line of defense against multidrug-resistant (MDR) Gram-negative bacterial infections, yet it is restricted due to high drug resistance and toxicity. The combination therapy of colistin and niclosamide exhibits excellent synergistic antibacterial activity against Gram-negative bacteria. How to co-deliver these two drugs with vastly different pharmacokinetic properties in sufficient amounts to the infection site is the core issue that must be resolved for the clinical translation of this drug combination. Here, we designed and prepared a nanosystem capable of co-loading colistin and niclosamide with different physicochemical properties into mPEG-PLGA nanoparticles (COL/NIC-mPEG-PLGA-NPs) to overcome the resistance of multiple colistin-resistant bacteria to colistin and alleviate its toxicity. Mechanistic studies revealed that the COL/NIC-mPEG-PLGA-NPs enhanced the affinity of delivered COL to the modified membrane of colistin-resistant bacteria. The increased membrane permeability caused by colistin promotes an influx of niclosamide, which reduces efflux pump activity and generates intracellular ROS stress, eliminating colistin-resistant bacteria. In addition, the nanoparticles proved non-toxic both in vitro and in vivo. Overall, our study has profound insights into the use of nanosystems with high biosafety for the treatment of infections caused by colistin-resistant bacteria.https://doi.org/10.1038/s42003-025-08095-8 |
| spellingShingle | Kaifang Yi Xilong Wang Pengliang Li Yanling Gao Dandan He Yushan Pan Xiaoyuan Ma Gongzheng Hu Yajun Zhai Amphiphilic mPEG-PLGA copolymer nanoparticles co-delivering colistin and niclosamide to treat colistin-resistant Gram-negative bacteria infections Communications Biology |
| title | Amphiphilic mPEG-PLGA copolymer nanoparticles co-delivering colistin and niclosamide to treat colistin-resistant Gram-negative bacteria infections |
| title_full | Amphiphilic mPEG-PLGA copolymer nanoparticles co-delivering colistin and niclosamide to treat colistin-resistant Gram-negative bacteria infections |
| title_fullStr | Amphiphilic mPEG-PLGA copolymer nanoparticles co-delivering colistin and niclosamide to treat colistin-resistant Gram-negative bacteria infections |
| title_full_unstemmed | Amphiphilic mPEG-PLGA copolymer nanoparticles co-delivering colistin and niclosamide to treat colistin-resistant Gram-negative bacteria infections |
| title_short | Amphiphilic mPEG-PLGA copolymer nanoparticles co-delivering colistin and niclosamide to treat colistin-resistant Gram-negative bacteria infections |
| title_sort | amphiphilic mpeg plga copolymer nanoparticles co delivering colistin and niclosamide to treat colistin resistant gram negative bacteria infections |
| url | https://doi.org/10.1038/s42003-025-08095-8 |
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