A Hemoglobin Bionics‐Based System for Combating Antibiotic Resistance in Chronic Diabetic Wounds via Iron Homeostasis Regulation

Abstract

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, we aim to propose an effective therapy based on hemoglobin bionics to induce disturbances in bacterial iron homeostasis. The preferred “iron cargo” was synthesized by protoporphyrin IX chelated with dopamine and gallium (PDGa), and was delivered via a glucose/pH‐responsive microneedle bandage (PDGa@GMB). The PDGa@GMB down‐regulated 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 demonstrated insusceptibility to genetic resistance while maintaining sustainable antimicrobial effects (> 90%) against resistant strains of both S. aureus and E. coli, and accelerated 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.This article is protected by copyright. All rights reserved