Bioresponsive nano-antibacterials for H ₂ S-sensitized hyperthermia and immunomodulation against refractory implant–related infections

Abstract

There is an increasingly growing demand for nonantibiotic strategies to overcome drug resistance in bacterial biofilm infections. Here, a novel “gas-sensitized hyperthermia” strategy is proposed for appreciable bacteria killing by the smart design of a metal-organic framework (MOF)–sealed Prussian blue–based nanocarrier (MSDG). Once the biofilm microenvironment (BME) is reached, the acidity-activated MOF degradation allows the release of diallyl trisulfide and subsequent glutathione-responsive generation of hydrogen sulfide (H 2 S) gas. Upon near-infrared irradiation, H 2 S-sensitized hyperthermia arising from MSDG can efficiently eliminate biofilms through H 2 S-induced extracellular DNA damage and heat-induced bacterial death. The generated H 2 S in the biofilm can stimulate the polarization of macrophages toward M2 phenotype for reshaping immune microenvironment. Subsequently, the secretion of abundant regeneration-related cytokines from M2 macrophages accelerates tissue regeneration by reversing the infection-induced pro-inflammatory environment in an implant-related infection model. Collectively, such BME-responsive nano-antibacterials can achieve biofilm-specific H 2 S-sensitized thermal eradiation and immunomodulatory tissue remodeling, thus realizing the renaissance of precision treatment of refractory implant–related infections.

Surface-Confined Piezocatalysis Inspired by ROS Generation of Mitochondria Respiratory Chain for Ultrasound-Driven Noninvasive Elimination of Implant Infection

“…Moreover, bacterial antibiotic resistance and persistent infections on implant surfaces can be facilitated by the biofilm formation process. 34 It was also found that the piezoPCL US(+) group had a more significant antibiofilm formation compared with the other groups (Figure S13). More importantly, there were no significant changes of antibacterial performance between the pristine and aged samples after about 12 months of storage (Figure S14).…”

“…We then measured the US-induced temperature changes of piezoPCL and its effect on the bacterial-killing process, and the sonothermal effect of piezoPCL was found to be negligible against the bacteria killing (Figure S12). Moreover, bacterial antibiotic resistance and persistent infections on implant surfaces can be facilitated by the biofilm formation process . It was also found that the piezoPCL US­(+) group had a more significant antibiofilm formation compared with the other groups (Figure S13).…”

Designing Single‐Atom Active Sites on sp2‐Carbon Linked Covalent Organic Frameworks to Induce Bacterial Ferroptosis‐Like for Robust Anti‐Infection Therapy

“…We attempted to explain this behavior by immunofluorescent double staining of CD80 and CD160, as it was previously reported to be related to M2 macrophage polarization. [ 52 ] In this regard, visual examination of the stained images and quantitative results revealed that the Ir and Ru SACs possess the minimum number of CD86 + proinflammatory M1 macrophages and the maximum number of CD206 + anti‐inflammatory M2 macrophages (Figure 8f,i,j). Our result confirmed that our final formulation plays a functional role in suppressing inflammatory responses and immunoregulation in abscess healing through this hypothetical pathway, achieving the initiation of the proliferative phase of the healing cascade.…”

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

“…[11] This BME can suppress the host antibacterial immunity via polarizing primary macrophages (M0) to the anti-inflammatory phenotype (M2). [12][13][14] The established biofilms not only block the traditional antibiotics but also assist bacterial immune escape, thus leading to the failure of conventional single antibacterial strategies. [15] Therefore, enhancing the efficacy of anti-biofilm therapy and weakening bacterial biofilm immune resistance are currently the main strategies for treating BAIs.…”