A remotely controlled nanotherapeutic with immunomodulatory property for MRSA-induced bone infection

Abstract

Osteomyelitis is a deep bone tissue infection caused by pathogenic microorganisms, with the primary pathogen being methicillin-resistant Staphylococcus aureus (MRSA). Due to the tendency of the infection site to form biofilms that shield drugs and immune cells to kill bacteria, combined with the severe local inflammatory response causing bone tissue destruction, the treatment of osteomyelitis poses a significant challenge. Herein, we developed a remotely controlled nanotherapeutic (TLBA) with immunomodulatory to treat MRSA-induced osteomyelitis. TLBA, combined with baicalin and gold nanorods, is positively charged to actively target and penetrate biofilms. Near-infrared light (808 nm) triggers spatiotemporal, controllable drug release, while bacteria are eliminated through synergistic interaction of non-antibiotic drugs and photothermal therapy, enhancing bactericidal efficiency and minimizing drug resistance. TLBA eliminated nearly 100 % of planktonic bacteria and dispersed 90 % of biofilms under NIR light stimulation. In MRSA-induced osteomyelitis rat models, laser irradiation raised the infection site temperature to 50 °C, effectively eradicating bacteria, promoting M2 macrophage transformation, inhibiting bone inflammation, curbing bone destruction, and fostering bone tissue repair. In summary, TLBA proposes a more comprehensive treatment strategy for the two characteristic pathological changes of bacterial infection and bone tissue damage in osteomyelitis.