Ultrasound Molecular Imaging Enhances High‐Intensity Focused Ultrasound Ablation on Liver Cancer With B7‐H3‐Targeted Microbubbles

BACKGROUND: High-intensity focused ultrasound (HIFU) is a promising minimally invasive treatment for liver cancer; however, its efficacy is often limited by the attenuation of ultrasonic energy. This study investigates the effectiveness of B7-H3-targeted microbubbles (T-MBs) in enhancing HIFU ablation of liver cancer and explores their potential for clinical translation. METHODS: T-MBs and isotype control microbubbles (I-MBs) were synthesized through the conjugation of biotinylated anti-B7-H3 antibody and isotype control antibody to the microbubble surface, respectively. Contrast-enhanced ultrasound imaging was performed to compare the accumulation of T-MBs and I-MBs in liver cancer at various time points. The efficacy of T-MBs in enhancing HIFU treatment was evaluated by measuring the immediate tumor ablation rate and long-term tumor growth suppression. Additionally, the induced antitumor immune response was assessed through cytokine quantification in serum and tumor tissue, along with immunofluorescence staining conducted on days 1, 3, and 7 post-treatment. RESULTS: T-MBs demonstrated superior liver cancer-specific accumulation, characterized by higher concentrations and prolonged retention compared to I-MBs. The combination of T-MBs with HIFU resulted in significantly enhanced tumor ablation rates and superior tumor growth suppression. Post-treatment analysis revealed a gradual uptick in cytokine levels within the tumor microenvironment, along with progressive infiltration of antitumor immune cells. CONCLUSION: T-MBs effectively enhance the therapeutic efficacy of HIFU for liver cancer treatment while simultaneously promoting an antitumor immune response. These findings provide a strong experimental foundation for the clinical translation of ultrasound molecular imaging combined with HIFU as a novel approach for tumor therapy.