Abstract
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), CoFe(2)O(4)@MnFe(2)O(4) 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.