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@MnFe2O4) 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@MnFe2O4. Overall, QSIAT provides a universal enhancement strategy for amplifying the bactericidal effects of conventional therapy via stress response interference. A magnetic hyperthermia amplifier, hyaluronic acid-coated ferrite (HA@MnFe2O4) is developed for recalcitrant biofilm treatment. The nanomedicine is based on a synergistic therapeutic strategy involving quorum sensing interference assisted therapy (QSIAT) and immunomodulation. The exceptional biofilm removal and anti-inflammatory effects of HA@MnFe2O4 highlight the promising future clinical application of QSIAT in tackling persistent biofilm infections.image