Multifunctional Fe3O4@ZIF-8 Nanoparticles with Antibiosis and Osteogenesis for Treatment of Jaw Osteomyelitis

<b>Background/Objectives</b>: Jaw osteomyelitis (OM) is a refractory purulent inflammation caused by bacterial infection, characterized by persistent infection, excessive bone resorption, and resultant bone defects. Currently, mainstream therapies for jaw OM struggle to eradicate persistent infections, avoid antibiotic resistance, and repair infected bone defects, posing a critical challenge in clinical practice. <b>Methods</b>: Herein, the Fe₃O₄@ZIF-8 core-shell nanoparticles (NPs) platform designed for jaw OM treatment consisted of Fe₃O₄ as the core and zeolitic imidazolate framework-8 (ZIF-8) as the shell. <b>Results</b>: The core-shell platform not only integrated the pH-responsive degradation capability of ZIF-8 but also retained the superparamagnetism of Fe₃O₄ NPs. In the acidic, infectious microenvironment, Fe₃O₄@ZIF-8 NPs underwent continuous degradation, releasing Zn²⁺, thereby conferring potent antibacterial activity. The specific antibacterial mechanism of the nanoparticles lies in the fact that high concentrations of Zn²⁺ directly disrupted bacterial cell membranes and inhibited the bacterial heat shock response. This dysregulates bacterial proteostasis, rendering the bacteria more sensitive to external adverse stresses, ultimately leading to bacterial death. With ZIF-8 framework degradation, the encapsulated Fe₃O₄ NPs were released. Under static magnetic field (SMF) synergy, Fe₃O₄ NPs collaborated with Zn²⁺ to promote bone regeneration and repair infected bone defects in jaw OM lesions. <b>Conclusions</b>: As a multifunctional core-shell platform, Fe₃O₄@ZIF-8 NPs meet the dual clinical needs of antibiosis and osteogenesis, offering a promising translational strategy for jaw OM therapy.