Volume 5 Number 1 2026
Ultrasound-activated nanoparticles for sonodynamic and immune therapy of liver cancer
Saba Zafar 1*
Biosensors and Nanotheranostics 5 (1) 1-8 https://doi.org/10.25163/biosensors.5110988
Submitted: 10 June 2026 Revised: 13 August 2026 Accepted: 14 August 2026 Published: 14 August 2026
Hepatocellular carcinoma (HCC) remains one of the most lethal solid tumors, and the deep, poorly accessible location of the liver blunts many of the treatments that work elsewhere. Sonodynamic therapy (SDT) has drawn growing attention precisely because ultrasound does what light cannot: it reaches centimeters into tissue and switches on a sonosensitizer only where the beam is focused. This review traces how that physical advantage has been married to nanotechnology to produce acoustic nanomedicines for HCC. We first revisit the biophysics—acoustic cavitation, sonoluminescence, pyrolysis, and reactive oxygen species (ROS) generation—that converts an acoustic pulse into oxidative injury. We then examine how engineered platforms, from porphyrin-loaded carriers to inorganic semiconductors and metal–organic frameworks, overcome the poor solubility and rapid clearance of early sonosensitizers. Particular weight is given to the hostile hepatic tumor microenvironment, where hypoxia and glutathione scavenging suppress ROS, and to the catalytic nanozymes, oxygen carriers, and vasodilator strategies devised to relieve it. Beyond direct killing, SDT emerges as a reliable trigger of immunogenic cell death, turning immunologically cold liver tumors responsive to checkpoint blockade. Finally, we consider multimodal theranostic guidance and the translational gaps—dosimetry, biosafety, and realistic preclinical models—that still separate promising mouse data from clinical liver oncology. Taken together, the evidence suggests sonodynamic nanomedicine is maturing, though unevenly.
Keywords: hepatocellular carcinoma; sonodynamic therapy; nanomedicine; reactive oxygen species; tumor microenvironment; immunogenic cell death; theranostics; ultrasound
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