Nanotechnology-assisted thermal ablation for hepatocellular carcinoma: Focus on radiofrequency and microwave ablation

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality. Radiofrequency ablation (RFA) and microwave ablation (MWA) are established local therapies for early-stage and selected intermediate-stage HCC, but their efficacy is limited by heat-sink-related underheating, uncertain margin delineation, and post-ablation microenvironmental remodeling that favors residual disease and recurrence.

This review summarizes nanotechnology-assisted strategies designed to improve RFA/MWA for HCC. We focus on nanoplatforms that enhance energy deposition, support image-guided margin assessment, and modulate post-ablation immune and metabolic responses, while critically appraising clinical feasibility, safety, and translational barriers.

Nanomaterials can improve thermal sensitization by increasing local energy absorption, heat retention, cavitation, vascular occlusion, or microwave coupling, thereby reducing incomplete ablation. Imaging-enabled platforms based on magnetic resonance, computed tomography, ultrasound, fluorescence, or positron emission tomography can help identify residual viable tumor and define ablation margins. Immunomodulatory platforms further amplify immunogenic cell death, antigen capture, stimulator of interferon genes (STING) signaling, checkpoint blockade, myeloid reprogramming, metabolic remodeling, and epithelial-mesenchymal transition suppression, potentially converting transient local inflammation into more durable antitumor immunity.

Nanotechnology should be viewed as a functional enhancer of RFA/MWA rather than an independent ablation modality. Translation requires procedure-compatible and image-guided delivery, integration with transarterial chemoembolization or immunotherapy, biomarker-based patient selection, standardized margin-assessment endpoints, recurrence-free survival outcomes, and rigorous safety/manufacturing evaluation.