Biofilm Homeostasis Interference Therapy via ¹O₂‐Sensitized Hyperthermia and Immune Microenvironment Re‐Rousing for Biofilm‐Associated Infections Elimination

Abstract

The recurrence of biofilm‐associated infections (BAIs) remains high after implant‐associated surgery. Biofilms on the implant surface reportedly shelter bacteria from antibiotics and evade innate immune defenses. Moreover, little is currently known about eliminating residual bacteria that can induce biofilm reinfection. Herein, novel “interference‐regulation strategy” based on bovine serum albumin–iridium oxide nanoparticles (BIONPs) as biofilm homeostasis interrupter and immunomodulator via singlet oxygen (1O2)‐sensitized mild hyperthermia for combating BAIs is reported. The catalase‐like BIONPs convert abundant H2O2 inside the biofilm‐microenvironment (BME) to sufficient oxygen gas (O2), which can efficiently enhance the generation of 1O2 under near‐infrared irradiation. The 1O2‐induced biofilm homeostasis disturbance (e.g., sigB, groEL, agr‐A, icaD, eDNA) can disrupt the sophisticated defense system of biofilm, further enhancing the sensitivity of biofilms to mild hyperthermia. Moreover, the mild hyperthermia‐induced bacterial membrane disintegration results in protein leakage and 1O2 penetration to kill bacteria inside the biofilm. Subsequently, BIONPs‐induced immunosuppressive microenvironment re‐rousing successfully re‐polarizes macrophages to pro‐inflammatory M1 phenotype in vivo to devour residual biofilm and prevent biofilm reconstruction. Collectively, this 1O2‐sensitized mild hyperthermia can yield great refractory BAIs treatment via biofilm homeostasis interference, mild‐hyperthermia, and immunotherapy, providing a novel and effective anti‐biofilm strategy.

Construction of Mn–N–C nanoparticles with multienzyme-like properties and photothermal performance for the effective treatment of bacterial infections

“…As a protective aggregate of bacteria, biofilms can make general bactericides ineffective or require a dramatic increase in dosage, and thus bacteria multiply and grow under the protection of a biofilm, which is directly responsible for the development of drug resistance in bacteria. 44 Nanozymes can disrupt the integrity of biofilms, leading to bacterial death through severe changes in the bacterial morphology. The destructive effect of Mn–N–C NPs + H 2 O 2 on MRSA biofilms was evaluated by adopting the crystal violet (CV) staining method (Fig.…”

Balancing Bioresponsive Biofilm Eradication and Guided Tissue Repair via Pro-Efferocytosis and Bidirectional Pyroptosis Regulation during Implant Surgery

“…34 The results demonstrated a notable elevation in the PI-positive rate respectively (Figures 4d and S17). 35,36 The results of CLSM showed strong red fluorescence in the PB + NIR and PCZs + NIR groups, indicating a significant presence of dead bacteria within the biofilm structure. The analysis of SEM further demonstrated a notable reduction in the bacterial quantity within both treatment groups.…”

The potential use of nanozymes as an antibacterial agents in oral infection, periodontitis, and peri-implantitis

“…Following this, the immunosuppressive microenvironment re-rousing induced by BIONPs effectively re-orients macrophages to adopt a pro-inflammatory M1 phenotype in vivo, to consume any remaining biofilm, and to impede biofilm reconstruction. By combining 1 O 2 -sensitized mild hyperthermia, immunotherapy, biofilm homeostasis interference, and mild hyperthermia, this approach offers a novel and efficacious method for treating refractory BAIs [ 116 ].…”