Multimodal imaging-guided sonodynamic therapy for orthotopic liver cancer using a functionalized sonosensitizer

Liver cancer remains a significant global health challenge, with rising incidence rates and limited treatment options, underscoring the urgent need for innovative and effective therapeutic strategies. Sonodynamic therapy (SDT) stands as a promising non-invasive treatment technique, yet its advancement faces challenges due to difficulties in precisely co-localizing the tumor, sonosensitizers, and focused ultrasound (FUS). Additionally, the absence of feasible methods for in vivo detection of reactive oxygen species (ROS) hampers further research and development in this field. Herein, our study introduces a novel sonosensitizer, a phthalocyanine-conjugated mesoporous silicate nanoparticle loaded with allylhydrazine (PAMSN). We confirm that PAMSN not only amplifies the fluorescent signal of phthalocyanine (1.9-fold) but also generates nitrogen gas bubbles via the interaction between allylhydrazine (ALZ) and ROS. This distinct attribute positions PAMSN as a versatile multimodal contrast agent suitable for in vivo tumor imaging and SDT applications. Moreover, we establish a FUS platform that integrates fluorescent and ultrasonic imaging guidance, ensuring the precise delivery of ultrasound to the targeted area. In conjunction with PAMSN, this platform can effectively treat orthotopic liver cancer in a murine model while in vivo monitoring of ROS and detection of cavitation are enabled. In conclusion, PAMSN-mediated SDT with the multimodal imaging-guided SDT platform facilitates a precise and controllable SDT process, providing a promising tool for safer and more effective SDT in clinical tumor treatment.