An emodin-mediated multifunctional nanoplatform with augmented sonodynamic and immunoregulation for osteomyelitis therapy.

Emodin (ED), as a traditional Chinese medicine, possesses a variety of biological activities and is also one of natural sonosensitizer. Whether emodin could react with titanium dioxide to enhance the sonodynamic activity for safely treating osteomyelitis remains to be explored. Hence, an ED-conjugated Mn-doped titanium dioxide (TOM) nanorod array is designed and prepared on titanium to eliminate bacterial infections under ultrasound (US) treatment. The doping of Mn and the formation of an inorganic-organic interfacial between ED and TOM cause an imbalance in the interfacial charge and reduce the band gap of TOM, thereby increasing the production of reactive oxygen species (ROS) under US. The generated ROS effectively destroys the bacterial cell membrane, accelerating Mn ions intake and thereby inducing ferroptosis-like death of MRSA. Moreover, the hybrid coating activates cAMP and cGMP-PKG pathways to modulate M1 polarization of macrophages to display potent phagocytosis to bacteria. After eliminating the bacterial infection, the coating also can facilitate macrophage M2 polarization to promote osteogenic differentiation. Overall, the Chinese medicine enhanced sonodynamic and immunotherapy have great promise in treating bacterial-infected osteomyelitis.