Eradicating intracellular MRSA via targeted delivery of lysostaphin and vancomycin with mannose-modified exosomes
Intracellular methicillin-resistant Staphylococcus aureus (MRSA) is extremely difficult to remove by common antibiotics, leading to infection recurrence and resistance. Herein we report a novel exosome-based antibiotic delivery platform for eradicating intracellular MRSA, where mannosylated exosome...
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Veröffentlicht in: | Journal of controlled release 2021-01, Vol.329, p.454-467 |
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Hauptverfasser: | , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Intracellular methicillin-resistant Staphylococcus aureus (MRSA) is extremely difficult to remove by common antibiotics, leading to infection recurrence and resistance. Herein we report a novel exosome-based antibiotic delivery platform for eradicating intracellular MRSA, where mannosylated exosome (MExos) is employed as the drug carrier and preferentially taken up by macrophages, delivering lysostaphin (MExoL) and vancomycin (MExoV) to intracellular pathogens. Combination of MExoL and MExoV eradicated intracellular quiescent MRSA. Moreover, MExos rapidly accumulated in mouse liver and spleen, the target organs of intracellular MRSA, after intravenous (IV) administration. Thus, the MExos antibiotic delivery platform is a promising strategy for combating intracellular infection.
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•Mannosylated exosomes targeting macrophage were developed by the metabolic labeling and click chemistry.•This mannosylated exosome could enhance the delivery of antibiotics to intracellular pathogens.•Combination of vancomycin and lysostaphin loaded exosomes displayed pronounced eradication of intracellular quiescent MRSA.•These antibiotics loaded exosomes showed no toxicity.•The exosomes encapsulated antibiotics will reduced the dose of vancomycin, followed by decreased toxicity and resistance. |
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ISSN: | 0168-3659 1873-4995 |
DOI: | 10.1016/j.jconrel.2020.11.045 |