Integration of Silica Nanorattles with Manganese-Doped In₂S₃/InOOH to Enable Ultrasound-Mediated Tumor Theranostics

As a result of their radiation-free nature and deep-penetration ability, tumor theranostics mediated by ultrasound have become increasingly recognized as a modality with high potential for translation into clinical cancer treatment. The effective integration of ultrasound imaging and sonodynamic therapy (SDT) into one nanoplatform remains an enormous challenge yet to be fully resolved. Here, a novel theranostic system, consisting of rattle-type SiO₂ (r-SiO₂) loaded with Mn-doped In₂S₃/InOOH (SMISO), was designed and synthesized to enable an improved ultrasound imaging-guided therapy. With Mn-doped In₂S₃/InOOH (MISO) and a heterojunction structure, this novel sonosensitizer facilitates the generation of reactive oxygen species (ROS) for SDT. By coupling interfaces between the shell and core in rattle-type SiO₂, multiple reflections/scattering are generated, while MISO has high acoustic impedance. By integrating r-SiO₂ and MISO, the SMISO composite nanoparticles (NPs) increase the acoustic reflection and provide enhanced contrast for ultrasound imaging. Through the effective accumulation in tumors, which was monitored by B-mode ultrasound imaging in vivo, SMISO composite NPs effectively inhibited tumor growth without adverse side effects under ultrasound irradiation treatment. This work therefore provides a new approach to integrate a novel gas-free ultrasound contrast agent and a semiconductor sonosensitizer for cancer theranostics.