Bio-Responsive Sliver Peroxide-Nanocarrier Serves as Broad-Spectrum Metallo-β-lactamase Inhibitor for Combating Severe Pneumonia
© 2023 Wiley-VCH GmbH..
Metallo-β-lactamases (MBLs) represent a prevalent resistance mechanism in Gram-negative bacteria, rendering last-line carbapenem-related antibiotics ineffective. Here, a bioresponsive sliver peroxide (Ag2 O2 )-based nanovesicle, named Ag2 O2 BP-MT@MM, is developed as a broad-spectrum MBL inhibitor for combating MBL-producing bacterial pneumonia. Ag2 O2 nanoparticle is first orderly modified with bovine serum albumin and polydopamine to co-load meropenem (MER) and [5-(p-fluorophenyl)-2-ureido]-thiophene-3-carboxamide (TPCA-1) and then encapsulated with macrophage membrane (MM) aimed to target inflammatory lung tissue specifically. The resultant Ag2 O2 @BP-MT@MM effectively abrogates MBL activity by displacing the Zn2+ cofactor in MBLs with Ag+ and displays potent bactericidal and anti-inflammatory properties, specific targeting abilities, and great bioresponsive characteristics. After intravenous injection, the nanoparticles accumulate prominently at infection sites through MM-mediated targeting . Ag+ released from Ag2 O2 decomposition at the infection sites effectively inhibits MBL activity and overcomes the resistance of MBL-producing bacteria to MER, resulting in synergistic elimination of bacteria in conjunction with MER. In two murine infection models of NDM-1+ Klebsiella pneumoniae-induced severe pneumonia and NDM-1+ Escherichia coli-induced sepsis-related bacterial pneumonia, the nanoparticles significantly reduce bacterial loading, pro-inflammatory cytokine levels locally and systemically, and the recruitment and activation of neutrophils and macrophages. This innovative approach presents a promising new strategy for combating infections caused by MBL-producing carbapenem-resistant bacteria.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:36 |
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| Enthalten in: |
Advanced materials (Deerfield Beach, Fla.) - 36(2024), 11 vom: 14. März, Seite e2310532 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Hanqing [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.03.2024 Date Revised 15.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/adma.202310532 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Metallo-β-lactamases (MBLs) represent a prevalent resistance mechanism in Gram-negative bacteria, rendering last-line carbapenem-related antibiotics ineffective. Here, a bioresponsive sliver peroxide (Ag2 O2 )-based nanovesicle, named Ag2 O2 BP-MT@MM, is developed as a broad-spectrum MBL inhibitor for combating MBL-producing bacterial pneumonia. Ag2 O2 nanoparticle is first orderly modified with bovine serum albumin and polydopamine to co-load meropenem (MER) and [5-(p-fluorophenyl)-2-ureido]-thiophene-3-carboxamide (TPCA-1) and then encapsulated with macrophage membrane (MM) aimed to target inflammatory lung tissue specifically. The resultant Ag2 O2 @BP-MT@MM effectively abrogates MBL activity by displacing the Zn2+ cofactor in MBLs with Ag+ and displays potent bactericidal and anti-inflammatory properties, specific targeting abilities, and great bioresponsive characteristics. After intravenous injection, the nanoparticles accumulate prominently at infection sites through MM-mediated targeting . Ag+ released from Ag2 O2 decomposition at the infection sites effectively inhibits MBL activity and overcomes the resistance of MBL-producing bacteria to MER, resulting in synergistic elimination of bacteria in conjunction with MER. In two murine infection models of NDM-1+ Klebsiella pneumoniae-induced severe pneumonia and NDM-1+ Escherichia coli-induced sepsis-related bacterial pneumonia, the nanoparticles significantly reduce bacterial loading, pro-inflammatory cytokine levels locally and systemically, and the recruitment and activation of neutrophils and macrophages. This innovative approach presents a promising new strategy for combating infections caused by MBL-producing carbapenem-resistant bacteria | ||
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| 700 | 1 | |a Mao, Yanfei |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Min |e verfasserin |4 aut | |
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