Carbon dot-decorated Ni-MOF heterojunction sonozymes for enhanced sonodynamic-chemodynamic cancer therapy

In recent years, sonodynamic/chemodynamic therapy (SDT/CDT) has emerged as a promising ROS-dependent antitumor strategy owing to its noninvasiveness, suitability for deep-seated tumors, and favorable tumor selectivity. However, current sonosensitizer nanoplatforms are still hampered by low-efficiency ultrasound-triggered charge separation, insufficient ROS generation, and limited adaptability to the tumor microenvironment (TME). Herein, a carbon dot (CD)-loaded Ni-MOF composite sonozyme nanoplatform (CD/Ni-MOF) is developed to achieve cascade-amplified intratumoral ROS generation and enhanced SDT/CDT synergistic therapy. Owing to the interfacial electronic transfer mechanism between CDs and Ni-MOF, the incorporation of CDs markedly improves the spatial separation and directional transport of ultrasound-excited redox species, suppresses electron-hole recombination, and simultaneously enhances the enzyme-mimicking catalytic activity of Ni-MOF. Furthermore, CD/Ni-MOF enables cascade amplification of ROS production at tumor sites by accelerating the catalytic conversion of H₂O₂ into highly cytotoxic ROS and weakening intracellular antioxidant defense. Finally, under ultrasound irradiation, CD/Ni-MOF effectively induces oxidative damage in tumor cells and significantly suppresses tumor growth with favorable biocompatibility. This work provides an interfacial engineering strategy based on carbon dot-sensitized MOF sonozymes, offering a rational design framework for highly efficient SDT/CDT nanoplatforms that can overcome TME constraints.