Bimetallic doped carbon dot nanozymes for enhanced sonodynamic and nanocatalytic therapy

Conventional inorganic semiconductors are not suitable for acting as nanozymes or sonosensitizers for <i>in vivo</i> therapeutic nanomedicine owing to the lack of excellent biocompatibility. Biocompatible carbon dots (CDs) exhibit a variety of biological activities due to their adjustable size and surface chemical modification; however, the simultaneous sonodynamic activity and multiple enzyme-mimicking catalytic activity of a single CD have not been reported. Herein, we report the development of bimetallic doped CDs as a high-efficiency nanozyme and sonosensitizer for enhanced sonodynamic therapy (SDT) and nanocatalytic therapy (NCT). By selecting metal-organic complexes like EDTA-FeNa as the carbon source, we ensure that the coordination environments of metal atoms are preserved throughout the low-temperature calcination process. Compared with the single metal doped CDs including Fe-CDs or Ni-CDs, the obtained Fe and Ni co-doped CDs (Fe-Ni-CDs) not only exhibit enhanced sonodynamic activity owing to the decreased bandgap, but also possess augmented dual enzyme-mimicking catalytic activities due to the synergistic effect of bimetallic ions. The Fe-Ni-CD-mediated cascade amplification of ROS generation could lead to the production of ¹O₂ and O₂˙^- through SDT, the generation of ˙OH through POD-mimicking catalytic activity, and the provision of more O₂ for SDT through CAT-mimicking catalytic activity. Through the integrated multifunctionality of Fe-Ni-CDs, we successfully enhanced the effectiveness of antitumor treatment with a single drug injection and a single US irradiation for enhanced SDT and NCT. This work provides a distinct paradigm of endowing CDs with sonodynamic and multiple enzyme-mimicking catalytic activities for enhanced SDT and NCT through bimetallic ion doping.