A pH-responsive magnetic-controlled nanocomposite for precise and efficient vancomycin delivery in treating prosthetic joint infections

Abstract

Prosthetic joint infection (PJI) presents a significant medical challenge, with current surgical and antibiotic strategies often limited by high recurrence rates, the need for multiple interventions, and rising antibiotic resistance. This study introduces vancomycin-loaded magnetic iron oxide nanoparticles (IONPs) incorporated into ZIF-8-based nanocomposites, termed Van-IONPs@ZIF-8, designed to deliver antibiotics directly to the PJI infection site under an external magnetic field (MF) for targeted antibacterial therapy. The Van-IONPs@ZIF-8 demonstrated excellent pH sensitivity, in vitro biocompatibility, and marked antibacterial efficacy against Staphylococcus aureus. When subjected to an external MF, these magnetic nanocomposites effectively localized at infection sites. In vivo results indicated that the Van-IONPs@ZIF-8 + MF treatment significantly reduced bacterial loads on implants, decreased blood leukocyte counts, and mitigated inflammatory cell infiltration in surrounding tissues compared to controls. Concurrently, a marked reduction in both the number of pro-inflammatory cells and the levels of pro-inflammatory cytokines was observed, alongside a corresponding increase in inflammatory repair cells and reparative cytokines within the local tissues surrounding the infected implants. Thus, Van-IONPs@ZIF-8, in conjunction with an external MF, facilitates precise targeting of local infection sites and promotes rapid vancomycin release, representing a promising strategy for the safe and effective treatment of PJI.