Nanoscale Ruthenium Selenide-Mediated Photoacoustic Imaging-Guided Sonocatalytic Therapy for Hepatocellular Carcinoma

Abstract Hepatocellular carcinoma (HCC) is one of the most aggressive and fatal solid malignancies. It features an insidious early-stage progression, while advanced HCC lacks effective curative interventions. In this work, a ruthenium selenide (RuSe, RS) nanosonosensitizer was rationally fabricated for ultrasound (US)-activated sonocatalytic therapy for HCC treatment. Under US stimulation, the RS nanosonosensitizer triggers substantial intracellular reactive oxygen species overaccumulation, which disrupts mitochondrial membrane potential, consumes intracellular adenosine triphosphate and glutathione, and aggravates intracellular lipid peroxidation. The amplified oxidative stress further initiates and synergizes tumor cell apoptosis and ferroptosis, achieving suppression of HCC proliferation. Collectively, this study establishes a high-efficiency nanotheranostic paradigm for HCC management, which provides an avenue for accelerating the clinical translation of sonocatalytic tumor therapy.