Quorum Sensing Interference Assisted Therapy-Based Magnetic Hyperthermia Amplifier for Synergistic Biofilm Treatment.

Biofilms offer bacteria a physical and metabolic barrier, enhancing their tolerance to external stress. Consequently, these biofilms limit the effectiveness of conventional antimicrobial treatment. Recently, quorum sensing (QS) has been linked to biofilm's stress response to thermal, oxidative, and osmotic stress. Herein, a multiple synergistic therapeutic strategy that couples quorum sensing interference assisted therapy (QSIAT)-mediated enhanced thermal therapy with bacteria-triggered immunomodulation in a single nanoplatform, is presented. First, as magnetic hyperthermia amplifier, hyaluronic acid-coated ferrite (HA@MnFe2 O4 ) attenuates the stress response of biofilm by down-regulating QS-related genes, including agrA, agrC, and hld. Next, the sensitized bacteria are eliminated with magnetic heat. QS interference and heat also destruct the biofilm, and provide channels for further penetration of nanoparticles. Moreover, triggered by bacterial hyaluronidase, the wrapped hyaluronic acid (HA) decomposes into disaccharides at the site of infection and exerts healing effect. Thus, by reversing the bacterial tissue invasion mechanism for antimicrobial purpose, tissue regeneration following pathogen invasion and thermal therapy is successfully attained. RNA-sequencing demonstrates the QS-mediated stress response impairment. In vitro and in vivo experiments reveal the excellent antibiofilm and anti-inflammatory effects of HA@MnFe2 O4 . Overall, QSIAT provides a universal enhancement strategy for amplifying the bactericidal effects of conventional therapy via stress response interference.

Gold nanoclusters-loaded hydrogel formed by dimeric hydrogen bonds crosslinking: A novel strategy for multidrug-resistant bacteria-infected wound healing.

Restoring skin integrity after wound infection remains a tougher health challenge due to the uncontrolled antibiotic-resistant pathogens caused by antibiotic abuse. Herein, an injectable hydrogel with dual antibacterial and anti-inflammatory activities composed of gold nanoclusters (GNCs) and carbomer (CBM) is developed for wound dressing to overcome multidrug-resistant infection. Firstly, both experimental investigations and molecular dynamics simulation validate the protonation state of 6-mercaptohexanoic acid (MHA) ligands play an important role in its antibacterial action of GNCs. The self-organizing GNCs-CBM composite hydrogel is then spontaneously cross-linked by the dimeric hydrogen bonds (H-bonds) between the MHA ligands and the acrylic acid groups of CBM. Benefitting from the dimeric H-bonds, the hydrogel becomes thickening enough as an ideal wound dressing and the GNCs exist in the hydrogel with a high protonation level that contributes to the enhanced bactericidal function. In all, by combining bactericidal and immunomodulatory actions, the GNCs-CBM hydrogel demonstrated excellent synergy in accelerating wound healing in animal infection models. Hence, the dimeric H-bonds strengthening strategy makes the GNCs-CBM hydrogel hold great potential as a safe and effective dressing for treating infected wounds.