A Hemoglobin Bionics-Based System for Combating Antibiotic Resistance in Chronic Diabetic Wounds via Iron Homeostasis Regulation
© 2024 Wiley‐VCH GmbH.
| Publié dans: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 30 vom: 13. Juli, Seite e2405002 |
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| Auteur principal: | |
| Autres auteurs: | , , , , , |
| Format: | Article en ligne |
| Langue: | English |
| Publié: |
2024
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| Accès à la collection: | Advanced materials (Deerfield Beach, Fla.) |
| Sujets: | Journal Article diabetic wound healing glycemic regulation hemoglobin‐mimicking intelligent delivery system iron homeostasis Iron E1UOL152H7 Gallium CH46OC8YV4 plus... |
| Résumé: | © 2024 Wiley‐VCH GmbH. Owing to the increased tissue iron accumulation in patients with diabetes, microorganisms may activate high expression of iron-involved metabolic pathways, leading to the exacerbation of bacterial infections and disruption of systemic glucose metabolism. Therefore, an on-demand transdermal dosing approach that utilizes iron homeostasis regulation to combat antimicrobial resistance is a promising strategy to address the challenges associated with low administration bioavailability and high antibiotic resistance in treating infected diabetic wounds. Here, it is aimed to propose an effective therapy based on hemoglobin bionics to induce disturbances in bacterial iron homeostasis. The preferred "iron cargo" is synthesized by protoporphyrin IX chelated with dopamine and gallium (PDGa), and is delivered via a glucose/pH-responsive microneedle bandage (PDGaGMB). The PDGa@GMB downregulates the expression levels of the iron uptake regulator (Fur) and the peroxide response regulator (perR) in Staphylococcus aureus, leading to iron nutrient starvation and oxidative stress, ultimately suppressing iron-dependent bacterial activities. Consequently, PDGa@GMB demonstrates insusceptibility to genetic resistance while maintaining sustainable antimicrobial effects (>90%) against resistant strains of both S. aureus and E. coli, and accelerates tissue recovery (<20 d). Overall, PDGa@GMB not only counteracts antibiotic resistance but also holds tremendous potential in mediating microbial-host crosstalk, synergistically attenuating pathogen virulence and pathogenicity |
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| Description: | Date Completed 25.07.2024 Date Revised 30.08.2024 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.202405002 |