Tumor vascular occlusion by calcium-based thermosensitizer provokes continuous cavitation effect and thermal energy transition efficiency of radiofrequency ablation therapy

Radiofrequency ablation (RFA) therapy for hepatocellular carcinoma (HCC) suffers from incomplete ablation with tumor remnants, recurrence, and metastasis. To capture these matters, a calcium-based thermosensitizer (CBT) was constructed, which can swell the thermal ablation treatment. DMXAA was encapsulated within CaCO₃ nanoparticles and surface-modified using PEG. DMXAA @CBTNps emanates continuous cavitation to enhance the RFA effect, lower RFA power, and shorten the RFA time by responding to the acidic tumor microenvironment and releasing carbon dioxide bubbles. Ca²⁺ deposition to form calcification instigates the calcium death of the tumor and strengthens the thermal conductivity, wherein CBT fortifies the immunogenic cell death (ICD) of RFA. The vascular disruptor DMXAA is administered to the tumor site to impair the blood and nutrient supply to the tumor tissue. Calcium carbonate nanoparticles generate persistent carbon dioxide bubbles within the acidic microenvironment, leading to a sustained cavitation effect that enhances magneto-thermal conversion. This synergistic approach facilitates tumor vascular occlusion, thereby improving thermal ablation therapy. This strategy is different from previous thermal ablation treatments in that the CBT-released product Ca²⁺, the continuous cavitation effect of CO₂, and the vascular disrupting agent can accelerate the conversion of energy from electromagnetic energy to thermal energy and reduce the heat loss, which significantly amplifies the effect of thermal ablation treatment of HCC and intensifies ICD. Therefore, this research provides a promising avenue and therapeutic platform for clinical liver cancer treatment.