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

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), 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.

Erythrocyte membrane-enveloped molybdenum disulfide nanodots for biofilm elimination on implants via toxin neutralization and immune modulation

“…Therefore, more attention needs to be paid to reverse this unfavorable immune state to avoid an infection recurrence. Macrophages have a powerful phagocytic ability and possess dynamic plasticity, conferring them as the most promising target to enhance immune therapy [41]. Macrophages can differentiate into the M1 phenotype, facilitating bacterial elimination, or into the M2 phenotype, that is correlated with immune suppression and infection recurrence [42].…”

A drug-free strategy to combat bacterial infections with magnetic nanoparticles biosynthesized in bacterial pathogens

“…40,57 Hyperthermia using modified MNPs to enable biofilm penetration has been employed to kill bacteria. 58,59 To assess if the bacteria in the biofilms can form MNPs upon treatment with iron and zinc, we first prepared biofilms and treated them with iron and zinc precursors for 36 h. The treated biofilms were then exposed to an AMF for 30 min and the viability was evaluated using live/dead staining. The red staining observed in AMF exposed biofilms (Fig.…”

A Drug-free, Self-destruction Strategy to Combat Bacterial Infections by Using the Intrinsically formed Magnetic Nanoparticles in Bacterial Pathogens

“…As these are often associated with persistent infections, several nanotechnology based approaches have been attempted to prevent/destroy biofilms [25b, 41]. Hyperthermia using MNPs that have been modified to facilitate its penetration of biofilms have been employed to destroy biofilms [42] . To evaluate the MNP formation in biofilm, we prepared biofilms using S. aureus and E. coli and treated with Fe and Zn precursors for 36 h. The treated biofilms were exposed to AMF for 30 min and the viability was evaluated using live/dead staining with FDA/PI staining.…”