Magneto‐Based Synergetic Therapy for Implant‐Associated Infections via Biofilm Disruption and Innate Immunity Regulation

Implant‐associated infections (IAIs) are a common cause of orthopedic surgery failure due to microbial biofilm‐induced antibiotic‐resistance and innate immune inactivation. Thus, the destruction of microbial biofilm plays a key role in reducing IAIs. Herein, first, a magneto‐based synergetic therapy (MST) is proposed and demonstrated against IAIs based on biofilm destruction. Under an alternating magnetic field (AMF), CoFe2O4@MnFe2O4 nanoparticles (MNPs), with a rather strong magnetic hyperthermal capacity, can generate sufficient thermal effect to cause dense biofilm dispersal. Loosened biofilms provide channels through which nitrosothiol‐coated MNPs (MNP‐SNOs) can penetrate. Subsequently, thermosensitive nitrosothiols rapidly release nitric oxide (NO) inside biofilms, thus efficiently killing sessile bacteria under the magnetothermal effect of MNPs. More importantly, MNP‐SNOs can trigger macrophage‐related immunity to prevent the relapse of IAIs by exposing the infected foci to a consistent innate immunomodulatory effect. The notable anti‐infection effect of this nanoplatform is also confirmed in a rat IAI model. This work presents the promising potential of combining magnetothermal therapy with immunotherapy, for the effective and durable control and elimination of IAIs. This work originates a magneto‐based synergetic therapy (MST) strategy against implant‐associated infections (IAIs) based on nitrosated mercaptosuccinic acid (MSA)‐coated CoFe2O4@MnFe2O4 nanoparticles (MNP‐SNO) with excellent magnetic hyperthermal capacity, nitric oxide (NO) releasing efficiency, and innate immunomodulatory activity, which demonstrates the great potentials of magnetic nanomedicine for the durable control and elimination of IAIs.