Biofilm Microenvironment‐Responsive Self‐Assembly Nanoreactors for All‐Stage Biofilm Associated Infection through Bacterial Cuproptosis‐like Death and Macrophage Re‐Rousing

Abstract

Bacterial biofilm‐associated infections (BAIs) are the leading cause of prosthetic implant failure. The dense biofilm structure prevents antibiotic penetration, while the highly acidic and H2O2‐rich biofilm microenvironment (BME) dampens the immunological response of antimicrobial macrophages. Conventional treatments that fail to consistently suppress escaping planktonic bacteria from biofilm result in refractory recolonization, allowing BAIs to persist. Herein, a BME‐responsive copper‐doped polyoxometalate clusters (Cu‐POM) combination with mild photothermal therapy (PTT) and macrophage immune re‐rousing for BAI eradication at all stages is proposed. The self‐assembly of Cu‐POM in BME converts endogenous H2O2 to toxic ·OH through chemodynamic therapy (CDT) and generates a mild PTT effect to induce bacterial metabolic exuberance, resulting in loosening the membrane structure of the bacteria, enhancing copper transporter activity and increasing intracellular Cu‐POM flux. Metabolomics reveals that intracellular Cu‐POM overload restricts the TCA cycle and peroxide accumulation, promoting bacterial cuproptosis‐like death. CDT re‐rousing macrophages scavenge planktonic bacteria escaping biofilm disintegration through enhanced chemotaxis and phagocytosis. Overall, BME‐responsive Cu‐POM promotes bacterial cuproptosis‐like death via metabolic interference, while also re‐rousing macrophage immune response for further planktonic bacteria elimination, resulting in all‐stage BAI clearance and providing a new reference for future clinical application.

Urchin-like Fe3O4@Bi2S3 Nanospheres Enable the Destruction of Biofilm and Efficiently Antibacterial Activities

“…Besides, the persistent bacteria located in the inner layer of the biofilm displayed metabolic inactivity state, which caused incomplete eradication of bacteria and the relapse of biofilm infections. − Activating innate immunity to eliminate the persistent bacteria with inactive metabolism was an effective strategy to prevent infection recurrence. The polarization effect of Fe 3 O 4 @Bi 2 S 3 on RAW264.7 macrophages was carried out to determine the immune regulatory function.…”

Nanomaterials-Involved Tumor-Associated Macrophages’ Reprogramming for Antitumor Therapy

“…Moreover, self-assembly nanomaterials have also been advocated in TAMs’ reprogramming due to their high drug loading quantity, modifiability, and excellent biocompatibility. Xie et al reported a DNA nanocluster that was self-assembled by double-stranded DNA vectors with loaded unmethylated cytosine-phosphate-guanine (CpG) oligonucleotide (ODN) . The loaded CpG-ODN can bind with toll-like receptor 9 (TLR9) to stimulate immunocompetent cells for TAMs’ pro-inflammatory polarization and cancer immunotherapy. , High condensation of DNA nanoclusters could effectively protect CpG-ODNs from digestion and degradation by nuclease.…”

Vanadium Carbide MXenzyme Harnessing Photothermal Effects for Targeted Lung Tumor Suppression and Inflammation Eradication

“…Activated macrophages and dendritic cells foster the activation and expansion of T cells and release pro-inflammatory factors and stress proteins, facilitating immune cell-mediated killing of cancer cells. [37] However, an excessive inflammatory response may result in adverse treatment effects, causing infiltration and damage of immune cells in normal tissues, thus compromising the therapeutic outcome. Hence, suppressing PTT-induced inflammation may minimize harm to normal tissues and enhance treatment effectiveness.…”