Bimetallic doped carbon dot nanozymes for enhanced sonodynamic and nanocatalytic therapy

Conventional inorganic semiconductors are not suitable for acting as nanozymes or sonosensitizers for in vivo 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.