Space-Selective Chemodynamic Therapy of CuFe₅O₈ Nanocubes for Implant-Related Infections

Abstract

Implant-related infections (IRIs) are a serious complication after orthopedic surgery, especially when a biofilm develops and establishes physical and chemical barriers protecting bacteria from antibiotics and the hosts local immune system. Effectively eliminating biofilms is essential but difficult, as it requires not only breaking the physical barrier but also changing the chemical barrier that induces an immunosuppressive microenvironment. Herein, tailored to a biofilm microenvironment (BME), we proposed a space-selective chemodynamic therapy (CDT) strategy to combat IRIs using metastable CuFe5O8 nanocubes (NCs) as smart Fenton-like reaction catalysts whose activity can be regulated by pH and H2O2 concentration. In the biofilm, extracellular DNA (eDNA) was cleaved by high levels of hydroxyl radicals (•OH) catalyzed by CuFe5O8 NCs, thereby disrupting the rigid biofilm. Outside the biofilm with relatively higher pH and lower H2O2 concentration, lower levels of generated •OH effectively reversed the immunosuppressive microenvironment by inducing pro-inflammatory macrophage polarization. Biofilm fragments and exposed bacteria were then persistently eliminated through the collaboration of pro-inflammatory immunity and •OH. The spatially selective activation of CDT and synergistic immunomodulation exerted excellent effects on the treatment of IRIs in vitro and in vivo. The anti-infection strategy is expected to provide a method to conquer IRIs.

A Biofilm Microenvironment‐Activated Single‐Atom Iron Nanozyme with NIR‐Controllable Nanocatalytic Activities for Synergetic Bacteria‐Infected Wound Therapy

“…Similar to the TME, the biofilm microenvironment is characterized as low pH (4.5-6.5), H 2 O 2 overproduction, hypoxia and nutrient depletion. [9,38] Therefore, in order to in-depth investigate the excellent peroxidase catalytic property of the FePN SAzyme might originate from the most toxic •OH generation by Fenton-like reaction, which is important to induce the bacteria apoptosis for biofilm-infected chemodynamic therapy. P-Phthalic acid (TA) was first employed as a trapping probe to monitor the •OH generation by forming a highly fluorescent product, 2-hydroxy TA.…”

Self‐Amplification Immunomodulatory Strategy for Tissue Regeneration in Diabetes Based on Cytokine‐ZIFs System

“…M1 macrophages express most inducible nitric oxide synthase (iNOS) and surface markers CCR7 and CD86, and secrete pro‐inflammatory cytokines (interleukin‐6 (IL‐6), tumor necrosis factor (TNF‐α), and interleukin‐12), which facilitate the elimination of microorganisms but also lead to the pathologic type 1 inflammation response in diabetes. [ 10a,19 ] M2 macrophages, in contrast, can relieve type 1 inflammatory responses, promoting cell proliferation, angiogenesis, and tissue regeneration by abundant expression of arginases‐1 (Arg‐1), surface markers CD206 and CD163, anti‐inflammatory factors (IL‐4, IL‐10, and IL‐13), and tissue regeneration mediators (vascular endothelial growth factor (VEGF) and BMP‐2). [ 2a,3,10a,12a,19 ]…”

“…[ 10a,19 ] M2 macrophages, in contrast, can relieve type 1 inflammatory responses, promoting cell proliferation, angiogenesis, and tissue regeneration by abundant expression of arginases‐1 (Arg‐1), surface markers CD206 and CD163, anti‐inflammatory factors (IL‐4, IL‐10, and IL‐13), and tissue regeneration mediators (vascular endothelial growth factor (VEGF) and BMP‐2). [ 2a,3,10a,12a,19 ]…”

Recent Advances in Nanomaterial‐Based Nanoplatforms for Chemodynamic Cancer Therapy

“…Currently, numerous literatures have been illustrated that metal oxide can be used as Fenton nanocatalysts for cancer treatment. [27] Increasing H 2 O 2 content is beneficial for improving the efficiency of Fenton/Fenton-like reaction. Given that, peroxide nanodots have also been utilized in chemodynamic cancer therapy as H 2 O 2 self-suppliers.…”